List of Experiments

Brookhaven National Laboratory

BNL-1. Effectiveness of Iodine-131 in Diagnosing and Treating Graves = Disease  and Metastatic Carcinoma of the Thyroid

IN 1950, BROOKHAVEN National Laboratory conducted a study on the use of iodine­131 (I¹³¹) to treat patients with metastatic carcinoma of the thyroid or with Graves=disease. Patients for the study were sent to Brookhaven from Memorial Hospital in New York City.

In the study, a therapeutic dose of 4 to 360 millicuries of I¹³¹ was given to the patients; the exact dose depended in part on the number of metastases and on previous radiation treatment. Graves=disease patients who were unsuitable for surgical therapy were treated with I¹³¹ in doses of 6 to 20 millicuries. The patients were monitored for hematological damage. Metabolic studies were also conducted, including study of the effects of radiation dose on renal tubular function. Twelve patients participated in the study, ranging in age from 15 to 63 years. Of the 12 patients, 8 were female. The study was conducted in conjunction with the Memorial Hospital and was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Farr, L.E. AObservations of Renal Function in Patients Receiving Internally Administered Radioactive Isotopes.@In Symposium on Radiobiology, A.A.A.S., Cleveland, Ohio. December 30, 1950. 

Memorandum. L.E. Farr to BNL Committee on Use of Radioactive Isotopes in Human Studies. January 20, 1950. Brookhaven National Laboratory Project H­1. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.

Memorandum. BNL Committee on Use of Radioactive Isotopes in Human Studies. January 20, 1950. Brookhaven National Laboratory Project H­1. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-2. Boron Neutron Capture Therapy

BROOKHAVEN NATIONAL LABORATORY conducted boron neutron capture therapy (BNCT) on 45 patients from 1951 to 1961. The patients all were suffering from aggressive and otherwise untreatable types of brain tumors, such as glioblastoma multiforme or malignant glioma; all had received conventional radiation treatments. The purpose of BNCT was to attack more precisely the tumors with radiation, destroying the tumor cells. The patients were injected with a discrete amount of boron that was intended to deposit in the tumor. The tumors were then bombarded with a beam of neutrons that was directed to the boron and thus aimed at destroying the tumor.

The results of this therapy were unsuccessful. Patients who were treated with BNCT generally lived only as long as those patients, with the same types of brain tumors, who were treated with conventional radiation therapies. This work was funded by the U.S. Atomic Energy Commission. Currently, advances in technology that deliver higher concentrations of boron to tumor tissues for potentially improved therapy have brought about the return of BNCT. As a result, Brookhaven is currently involved in BNCT research and clinical trials. (BNCT was referenced in the Markey report; this summary was included in The DOE Roadmap of February 1995, and since revised.)

References

Farr, L.E., W.H. Sweet, L.B. Locksley, and J.S. Robertson. ANeutron Capture Therapy of Gliomas Using Boron.@In Transactions of the American Neurological Association. 1954, pp. 110B113.

Farr, L.E., J.S. Robertson, and E. Stickley. AUse of the Nuclear Reactor for Neutron Capture Therapy of Cancer.@Presented at International Conference on the Peaceful Uses of Atomic Energy. June 23, 1955.

Farr, L.E., S.W. Lippincott, W. Kahle, W.B. Haymaker, and P. Yakovlev. AThe Neuropathological and Topographical Study of Whole Brains Following Neutron Capture Therapy for Glioblastoma Multiforme.@In Proc. III Congress Int=l de Neuropathologie, Acta Medica Belgica.1958, pp. 227B228.

Godwin, J.T., L.E. Farr, W.H. Sweet, and J.S. Robertson. APathological Study of Eight Patients with Glioblastoma Multiforme Treated by Boron Neutron Capture Therapy Using Boron 10.@Cancer. Vol. 8. No. 3, MayBJune 1955, pp. 601B615.

Lippincott, S.W., Y.L. Yamamoto, and L.E. Farr, ARadiation Effects of Neutron­Capture Therapy on a Malignant Vascular Neoplasm of the Cerebellum.@A.M.A. Archives of Pathology. Vol. 69, January 1960, pp. 44B54.

Slatkin, D.N. AA History of Boron Neutron Capture Therapy of Brain Tumors.@Brain. Vol. 114, 1991, pp. 1,609B1,629.

Letter. D.L. Sutherland to L.E. Farr. May 23, 1953. Brookhaven National Laboratory Project H­15. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.

Memorandum. L.E. Farr. February 26, 1951. Brookhaven National Laboratory Project H­15. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-3. Iodine-131 Used to Measure Thyroid Function in Young Children with Nephrotic Syndrome

SCIENTISTS AT BROOKHAVEN National Laboratory conducted a series of experiments using a group of young children suffering from nephrotic syndrome (kidney disease). In 1951, eight of these children, ages 2 to 6 years, with renal functions varying from 14 to 225 percent of normal and with varying degrees of edema or lack thereof, were studied after administration of iodine­131 (I¹³¹).

A uniform ability by the thyroid gland to extract radioactive iodine from the blood was noted. The maximum uptake by the gland varied from 30 to 60 percent of the administered doses, which ranged from 3 to 5 microcuries. These data were evaluated against comparable data obtained in normal children. The scientists concluded that there is no impairment of the thyroid gland in its ability to take up iodine in young children with the nephrotic syndrome. (Included in The DOE Roadmap of February 1995)

References

Farr, L.E., J.L. Gamble, C.G. Foster, and J.S. Robertson. AThyroid Function in Young Children with Nephrotic Syndrome.@Quarterly Progress Report April 1BJune 30, 1951. Upton, NY: Brookhaven National Laboratory, Medical Department, 1951, p. 119. Bldg. 490, Annual Periodic Reports.  "

BNL-4. Radioactive Chlorine, Bromine, and Sodium in Extracellular Fluids

FROM 1952 TO 1953, the total volume of extracellular fluids in 15 subjects was studied at Brookhaven National Laboratory. Five chronically ill hospital patients were injected with chlorine­38 (Cl³⁸) and sodium­24 (Na²⁴). Ten other patients were injected with Cl³⁸ and bromine­82 (Br⁸²). Total radiation doses were planned so that the weekly dose limit of 0.3 rad would not be exceeded. Blood samples were drawn at various times after injection and the radioactivity measured. During the course of this experiment, urine, red blood cells, pleural fluid, gastrointestinal fluid, and spinal fluid were also measured for Cl³⁸ and Br⁸². The subjects were considered to be Anormal@for purposes of this study. The U.S. Atomic Energy Commission funded this study. (Previously described in #3 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Gamble, J.L., J.S. Robertson, C.A. Hannigan, C.G. Foster, and L.E. Farr. Chloride, Bromide, Sodium, and Sucrose Spaces in Humans. Upton, NY: Brookhaven National Laboratory, BNL­1326, February 3, 1953. U.S. Department of Energy Archives, Record Group 326, U.S. Atomic Energy Commission, Division of Biology and Medicine, Box 3358, Folder 14.  "

BNL5. Measurement of the Turnover Rate of Sodium in Nephrotic Children Using Sodium-24

BROOKHAVEN NATIONAL LABORATORY conducted an experiment in 1954 on children suffering from nephrotic syndrome to study the rates of exchange of sodium in edema fluid, in ascitic fluid, and in the plasma. Sodium­24 (Na²⁴) as sodium chloride was injected intravenously and the plasma Na²⁴ disappearance curve was analyzed and compared to the Na²⁴ appearance curves in the two fluids. It was found that in both fluids the ratio of (a) the rate of change of the Na²⁴ concentration to (b) the difference between the Na²⁴ concentration in the plasma and that in the fluids, increased with time during the first few hours after injection. (Included in The DOE Roadmap of February 1995)

References

Robertson, J.S. AThe Turnover Rate of Sodium in Edema Fluid and Ascites.@In Federation Proceedings of the American Society for Experimental Pathology. Vol. 13, March 1954, p. 442.

Robertson, J.S. AThe Turnover Rate of Sodium in Edema Fluid and Ascites.@Quarterly Progress Report April 1BJune 30, 1954. Upton, NY: Brookhaven National Laboratory, Medical Department, 1954, p. 50. Bldg. 490, Annual Periodic Reports.  "

BNL-6. Degradation Rate of Iodine­131 B Labeled Normal Albumin Using the Whole-Body Gamma Spectrometer

IN 1954 , Brookhaven National Laboratory conducted metabolic studies in humans with iodine­131 (I¹³¹)­tagged serum albumin. In prior studies, plasma protein fractions labeled with I¹³¹ had been administered to normal subjects and to patients. A gamma spectrometer was constructed to determine transfer rates of locally injected I¹³¹ serum albumin and other substances tagged with gamma­emitting isotopes.

In this study, the biological half­time of I¹³¹­labeled human albumin was determined by two methods. The first method was the calculation from serum and urine samples following injection of 59 microcuries of I¹³¹. The second method used the whole-body gamma spectrometer to measure the amount of labeled albumin present in the body at stated intervals following injection of 6.6 microcuries of I¹³¹. Plasma­specific activity and urinary excretion were followed up to 60 days after injection. The rate of disappearance of the labeled albumin was measured in two patients. The first was a 49­year­old woman with chronic cystic mastitis; the second was a 40­year­old woman who had previously had a mastectomy. This research was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Cohn, S.H. AWhole-Body Counting.@Quarterly Progress Report April 1BJune 30, 1959. Upton, NY: Brookhaven National Laboratory, Medical Department, 1959, pp. 41B42. Bldg. 490, Annual Periodic Reports.

Lewallen, C.G. AStudies in Humans with I¹³¹ Serum Albumin.@Quarterly Progress Report July 1BSeptember 30, 1954. Upton, NY: Brookhaven National Laboratory, Medical Department, 1959, p. 51. Bldg. 490, Annual Periodic Reports.

Lippincott, S.W., S.H. Cohn, J.S. Robertson, and L.E Farr, AIn Vivo Measurement by the Whole-Body Gamma Spectrometer of the Degradation Rate of I¹³¹ Labeled Normal Albumin.@Laboratory Investigation. Vol. 10, Part 1, MayBJune 1961, pp. 481B491.  "

BNL-7. Studies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome

THIS STUDY WAS conducted at Brookhaven National Laboratory from 1955 to 1956. The subjects were six children in various phases of the nephrotic syndrome using iodine-131 (I¹³¹), including one child who had recovered from the illness, and nine normal subjects, consisting of eight men and one woman, all between the ages of 21 and 29 years. These subjects were given intravenous tracer doses of radioiodinated human plasma albumin and radioiodinated human gamma globulin. Three of the children were then given intravenous injections of radioiodinated human iron­binding globulin. The amount of activity administered was not to exceed 1.5 microcuries I¹³¹ per kilogram of body weight.

The disappearance of specific radioiodinated plasma protein from circulation and its cumulative appearance in the urine were studied; the urinary excretion of nonprotein radioiodine was also investigated. This study was supported by grants from the National Institutes of Health, the U.S. Public Health Service, the Muscular Dystrophy Association of America, the Playtex Park Research Institute, and the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Gitlin, D., C.A. Janeway, and L.E. Farr. AStudies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome. I. Albumin, Gamma Globulin, and Iron­Binding Globulin.@Quarterly Progress Report January 1BMarch 31, 1956. Upton, NY: Brookhaven National Laboratory, Medical Department, 1956, p. 52. Bldg. 490, Annual Periodic Reports.

Gitlin, D., C.A. Janeway, and L.E. Farr. AStudies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome: Albumin, Gamma Globulin and Iron­Binding Globulin.@Journal of Clinical Investigation. Vol. 35, JanuaryBJune 1956, pp. 44B56.

Gitlin, D., D.G. Cornwell, D. Nakasato, J.L. Oncley, W.L. Hughes, and C.A. Janeway. AStudies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome: The Lipoproteins.@Journal of Clinical Investigation.Vol. 37, No. 2, February 1958, pp. 172B184.

Memorandum. D. Gitlin to the BNL Committee for Use of Isotopes in Humans. July 15, 1954. Brookhaven National Laboratory Project H-37. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-8. Metabolism Studies with Acetate Labeled with Carbon-14

IN 1957 AND 1958, scientists at Brookhaven National Laboratory conducted studies to investigate carbon acetate metabolism. Forty to 200 microcuries of 1­C¹⁴Blabeled acetate or 2­C¹⁴Blabeled acetate were intravenously injected into subjects, including diabetics who had fasted and were denied insulin on the day of the experiment. Some of the subjects were cancer patients (nondiabetics); and others were patients with severe diabetes. More than 13 studies were conducted using various treatment combinations involving diet, fasting, insulin, or prednisone. The total number of subjects was about 20, both men and women, ranging in age from 12 to 60 years.

After medical staff administered the intravenous trace dose of C¹⁴­labeled acetate, metabolism products such as triglycerides, cholesterol, ketone bodies, glucose, pyruvic and alpha­ketoglutaric acids, and carbon dioxide were isolated from the blood, urine, and breath, and analyzed for C¹⁴ content. The study was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Hennes, A.R., and W.W. Shreeve. AHormonal Effects on C¹⁴ Acetate Metabolism in the Human.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 100, February 1959, pp. 246B250.

Shreeve, W.W., and A.R. Hennes. AEffect of Adrenal Steroid Hormones on the Metabolic Fate of C¹⁴­Labeled Acetate in Human Subjects.@Quarterly Progress Report July 1BSeptember 30, 1957. Upton, NY: Brookhaven National Laboratory, Medical Department, 1957. Bldg. 490, Annual Periodic Reports.

Shreeve, W.W., and A.R. Hennes. AEffect of Adrenal Steroid Hormones on the Metabolism of 2­C¹⁴­Pyruvate in Diabetic Humans.@Quarterly Progress Report July 1BSeptember 30, 1957. Upton: Brookhaven National Laboratory, Medical Department, 1957, pp. 36B37. Bldg. 490, Annual Periodic Reports.

Shreeve, W.W., A.R. Hennes, and R. Schwartz. AProduction of C¹⁴ from 1- and 2-C¹⁴ -Acetate by Human Subjects in Various Metabolic States.@Metabolism: Clinical and Experimental. Vol. 8, No. 5, 1959, pp. 741B756.  "

BNL-9. Metabolic Studies with Manganese-54

IN 1957, Brookhaven National Laboratory conducted human metabolic studies with the isotope manganese­54 (Mn⁵⁴). This study was the first to use Mn⁵⁴ in human subjects. Manganese had been assumed to participate indirectly in hematopoiesis (blood formation). Two or more patients were injected with Mn⁵⁴ and followed to determine count-rate at the body surface, blood radioactivity, and excretion rates. Blood taken from one of the patients 66 days after injection contained almost the entire radioactivity in the red cell fraction. This research was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Borg, D.C., G.C. Cotzias, and M. Birnbaum. ABasic Physiology of Manganese.@Quarterly Progress Report July 1BSeptember 30, 1957. Upton, NY: Brookhaven National Laboratory, Medical Department, 1957, p. 41. Bldg. 490, Annual Periodic Reports.

Borg, D.C., and G.C. Cotzias. AIncorporation of Manganese into Erythrocytes as Evidence for a Manganese Porphyrin in Man.@Nature. Vol. 182, December 13, 1958, pp. 1,677B1,678.  "

BNL-10. Magnesium Metabolism Studies in Humans with Magnesium-28

IN 1959, Brookhaven National Laboratory used magnesium­28 (Mg²⁸) to study the in vivo distribution and retention of magnesium in humans. Ten adults, 3 men and 7 women, were studied at the metabolic wards of the Brookhaven Medical Research Center Hospital. All but one of the men suffered from hypertension.

Nine of the subjects received intravenous injections of the isotope; two were studied after oral administration of Mg²⁸. The intravenous dosages, which ranged from 20 to 104 microcuries, were slowly administered to prevent toxic symptoms. Excretion rates were analyzed by measuring Mg²⁸ in urine and stool specimens. This study was conducted with support from the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Silver, L.J., J.S. Robertson, and L.K. Dahl. AMagnesium Turnover in the Human Studied with Mg²⁸.@Journal of Clinical Investigation. Vol. 39, February 1960, pp. 420B425.  "

BNL-11. Whole-Body Counting Technique Used to Study Turnover of Globulins Labeled with Iodine­131

IN 1959, Brookhaven National Laboratory conducted studies on the turnover of beta­ and gamma globulins labeled with iodine­131 (I¹³¹). The investigators used both the conventional method of blood and urine sampling and a new technique that used the whole-body gamma spectrometer. The new device allowed scientists to measure the retention of labeled globulins over long periods of time following administration of low levels of isotopes, particularly internally deposited gamma emitters.

One patient participated in these studies; he was placed in the whole-body counter 34 times. The subject was a multiple myeloma patient who was injected with the I¹³¹­labeled globulins on three occasions. The amount of iodine activity in the labeled globulins ranged from 17.0 to 50.16 microcuries. The study was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Lippincott, S.W., W.L. Hughes, and S. Korman. ATurnover of Labeled Globulins as Correlated with Serum Electrophoretic Pattern in Multiple Myeloma.@Bulletin of the Medical Department July 1, 1959. Upton, NY: Brookhaven National Laboratory, Medical Department, 1959, p. 16. Bldg. 490, Annual Periodic Reports.

Lippincott, S.W., S.H. Cohn, H. Hamel, S. Fine, and S. Korman. ADetermination of Radioactively Labeled Globulin Turnover by the Direct Whole-Body Counting Technique.@Journal of Clinical Investigation. Vol. 40, JanuaryBJune 1961, pp. 697B702.  "

BNL-12. A Study of Metabolic Pathways of Carbohydrate Formation Using Carbon-14

STUDIES WERE carried out at Brookhaven National Laboratory to study the metabolic pathways by which subjects in various metabolic states form glucose. In this study, the subjects were three men with bronchogenic carcinoma, three male diabetics, and one 13­year­old female diabetic. On the day of the experiment, the subjects were denied food and insulin and then were injected with C¹⁴­acetate. Carcinoma patients received 200 microcuries; diabetic patients received from 40 to 100 microcuries as a single 1­ to 2­minute injection. Breath samples were collected and analyzed. Some of these patients participated in multiple studies.

In a related study, two moderately diabetic subjects fasted and were orally administered 0.5 to 1.0 gram of C¹⁴­labeled ethanol per kilogram of body weight. The blood and urinary glucose were isolated. The results indicated that in one patient about 1 percent as much C¹⁴ was present in total-body glucose as had been excreted as CO₂ after 2.5 hours. In the other patient about 2 percent as much was present. Both patients had excreted about 25 percent of the total administered C¹⁴ by the end of 24 hours. This research was partly supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Shreeve, W.W., and M. Conovitz. AA Study of Metabolic Pathways of Carbohydrate Formation in Diabetes by Means of Carbon­14.@Quarterly Progress Report July 1BSeptember 30, 1955. Upton, NY: Brookhaven National Laboratory, Medical Department , 1955, p. 45. Bldg. 490, Annual Periodic Reports.

Shreeve, W.W., A.R. Hennes, and R. Schwartz. AProduction of C¹⁴O₂ from 1­ and 2­C¹⁴-Acetate by Human Subjects in Various Metabolic States.@Metabolism. Vol. 8, September 1959, pp. 741B756.  "

BNL-13. Analysis of Blood Glucose Following Intravenous Injection of Carbon-14

IN 1959, at Brookhaven National Laboratory, diabetic and nondiabetic patients were given intravenous injections of 40 to 150 microcuries of lactate or pyruvate labeled with carbon­14 (C¹⁴). The injections were followed by serial analysis of blood glucose for C¹⁴ content. Subsequently, glycogen was injected in an attempt to estimate relative glycogen labeling. Seven diabetic and three nondiabetic subjects were used in this study. The effects of insulin, tolbutamide, and glucose load were also studied in the same patients. This study was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

De Meutter, R.C. and W.W. Shreeve. AConversion of DL­Lactate­2-C¹⁴ or ­3-C¹⁴ or Pyruvate­2-C¹⁴ to Blood Glucose in Humans: Effects of Diabetes, Insulin, Tolbutamide, and Glucose Load.@Journal of Clinical Investigation. Vol. 42, No. 4, 1963, pp. 525B533.

Schwartz, R., R.C. DeMuetter, and W.W. Shreeve. ADynamics of Bicarbonate Movement and Turnover in Humans.@Quarterly Progress Report April 1BJune 30, 1959. Upton, NY: Brookhaven National Laboratory, BNL Medical Department, 1959, p. 52. Bldg. 490, Annual Periodic Reports.  "

BNL-14. The Metabolism and Fate of Tritiated Thymidine in Humans

THIS STUDY WAS CONDUCTED in 1959, at Brookhaven National Laboratory as part of an investigation of H³­thymidine as a label for DNA of proliferating cells in vivo and in vitro systems. In this study, H³­thymidine metabolism was studied in selected patients following intravenous injection. All patients were beyond reproductive age and were judged to have short life expectancies.

In two control patients with normal hematopoietic (blood­formation), thymidine labeled with tritium (H³) rapidly cleared the plasma and distributed in a volume as large as total-body water within a few minutes after injection. Two of the subjects selected for this initial investigation were patients with brain tumors, judged to have short life expectancies, and to be in hematopoietic equilibrium at the time of study. This research was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Cronkite, E.P., J.R. Rubini, S.A. Killmann, V.P. Bond, J. Bateman, L. Feinendegen, E. Adamik, L. Wood, M. Canner, M. Pavelec, and C. Sipe. AMetabolism of H³­Thymidine and H³­Labeled DNA.@Quarterly Progress Report April 1BJune 30, 1959. Upton, NY: Brookhaven National Laboratory, Medical Department, 1959, pp. 55B56. Bldg. 490, Annual Periodic Reports.

Rubini J.R., E.P Cronkite, V.P. Bond, and T.M. Fliedner. AThe Metabolism and Fate of Tritiated Thymidine in Man.@Journal of Clinical Investigation. Vol. 39, June 1960, pp. 909B918.   "

BNL-15. Study of Carbon-14 B Labeled Ascorbic Acid Metabolism

A RESEARCH COLLABORATION in the early 1970s between Brookhaven National Laboratory and Verwoerd Hospital in Pretoria, South Africa, resulted in a study of ascorbic acid (vitamin C) labeled with carbon­14 (C¹⁴) metabolism in Bantu tribesmen with a disease called hemosiderosis. This disease is similar to scurvy and is common among the South African Bantu. It involves excessive iron accumulation and failure to utilize ascorbic acid. This research was conducted to determine the metabolism of ascorbic acid.

Four adult Bantu men who had been diagnosed with hemosiderosis and scurvy participated in this study. Ascorbic acid labeled with carbon­14 was given orally, after which blood samples, urine samples, and respiratory CO₂ samples were collected and analyzed. The results indicated that most of the C¹⁴ was excreted primarily by respiration and secondarily in the urine. This work was jointly supported by the U.S. Atomic Energy Commission and the South African Atomic Energy Board. (Included in The DOE Roadmap of February 1995)

References

Hankes, L.V., C.R. Jansen, and M. Schmaeler. AAscorbic Acid Catabolism in Bantu with Hemosiderosis (Scurvy).@Biochemical Medicine. Vol. 9, 1974, pp. 244B255.  "

 ‡  ‡  ‡

BNL-16. Dose B Response Relationships Between Iodine-131 Administrations and Hematopoietic Effects

IN APPROXIMATELY 1951, physicians in the Medical Department of Brookhaven National Laboratory conducted a study to examine the relationship between the level of exposure to radiation from internally administered iodine-131 (I¹³¹) and the extent of radiation-induced effect to the hematopoietic (blood-cellBforming) system in exposed subjects. The scientists sought to determine a reliable indicator of I¹³¹ radiation-induced effect; the most accurate method of estimating the radiation dose delivered to tissue relative to the amount of I¹³¹ administered; and the predictability of a prior tracer study of the radiation dose delivered to the hematopoietic system by administration of a large amount of I¹³¹.

Study subjects were 33 patients with various metabolic rates associated with myxedema (a condition associated with a low thyroid activity), hypothyroid (slight depression of thyroid function), euthyroid (normal thyroid function), and hyperthyroid (overactivity of the thyroid). Some subjects had a history of prior I¹³¹ administrations in tracer or therapeutic amounts.

Subjects received tracer amounts of I¹³¹, followed a few weeks later in at least 18 cases by the administration of a therapeutic amount of I¹³¹, for total amounts of between 52 and 247 millicuries. All doses were administered orally. Blood and urine specimens were collected at intervals and analyzed for radioactivity. Differential white cell counts were obtained for at least 30 days after each I¹³¹ administration to monitor changes in the lymphocyte and neutrophil counts over time relative to pre-treatment.

The results suggested a that there was a reasonably good correlation between therapeutic amounts of I¹³¹ and the hematopoietic system response, and that the magnitude of the radiation dose to the hematopoietic system from any given amount is influenced by a variety of factors, primarily the individual=s metabolism of iodine.

The lymphocyte count was found to be the most sensitive and reliable measure of the magnitude of the radiation effect induced by exposure to I¹³¹. The fall in the lymphocyte count following administration of large amounts of I¹³¹ correlates well with the microcuries administered, but poorly with the integrated blood concentration of I¹³¹ together with a factor representing the integrated amount of I¹³¹ remaining in the body. This study was supported by the U.S. Atomic Energy Commission.

References

Ball, J.E., C.G. Foster, J. Robbins, R. Lazerson, L.E. Farr, and R.W. Rawson. ADosimetric Considerations in Determining Hematopoietic Damage from Radioactive Iodine.@American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. Vol. 70, No. 2, August 1953, pp. 274B282.

Memorandum. Brookhaven National Laboratory Committee on Use of Radioactive Isotopes in Human Subjects to J.S. Robertson. January 23, 1951. Brookhaven National Laboratory Project H-11, Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-17. Estimation of Body Water Volume and Potassium in Children Using Tritium and Potassium-42 as a Tracer

BETWEEN 1951 AND 1956, researchers in the Medical Department of Brookhaven National Laboratory conducted a physiological study to evaluate the use of water labeled with tritium (H³; tritiated water) in estimating total-body water and exchangeable potassium compared with an established antipyrine-based methodology. Study subjects included nine children ranging in age from 3 to 8 years, who were hospitalized in, or had been recently discharged from, the nephrotic unit at Brookhaven National Laboratory. All had protein in their urine, but eight were free of edema (swelling due to presence of abnormally large amounts of fluid in the spaces between cells of body tissues).

Three microcuries of potassium-42 (K⁴²) per kilogram of body weight, 75 microcuries of H³, and 400 milligrams of antipyrine in 10 milliliters of saline were administered simultaneously to each subject by intravenous infusion over a period of 1 hour. Blood samples for body water estimations were obtained from each subject at 2, 3, and 4 hours after infusion and continued at intervals up to 14 days. Urine samples also were obtained for H³ analysis. The data were used to examine the biological clearance of H³, H³ kinetics, and body water mixing, and to calculate and compare estimates of total-body water and exchangeable potassium based on H³ and antipyrine indications.

The results indicated that H³ equilibrium was completed in all subjects within 30 to 40 minutes of H³ infusion. Total body water volumes estimated using H³ were almost identical to those obtained using antipyrine. Estimates of exchangeable potassium obtained by either method ranged between 1.5 to 1.8 grams per liter per kilogram of body weight. This study was funded by the U.S. Atomic Energy Commission.

References

James, J.A., and J.S. Robertson. AEstimation of Exchangeable Water and Potassium by Radioisotope Dilution in Children.@American Medical Association Journal of Diseases of Children. Vol. 93, No. 3, March 1957, pp. 217B222.

Memorandum. J.S. Robertson to Brookhaven National Laboratory Committee on Use of Radioactive Isotopes in Human Subjects. January 23, 1951. Brookhaven National Laboratory Project H-12, Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-18. Cerebrospinal Fluid Studies Using Chlorine-38, Potassium-42, and Iodine-131

BETWEEN 1952 AND 1953, physicians in the Department of Surgery at Harvard University, the Department of Neurosurgery at Massachusetts General Hospital, and the Division of Medicine of Brookhaven National Laboratory collaborated on a study to examine the formation and cycling of cerebrospinal fluid. The two study subjects had histories of cerebrospinal fluid blockage as a result of spinal tumors. The blockages responded to surgical treatment in both cases. Potassium-42 (K⁴²) and chlorine-38 (Cl³⁸) were selected as dual tracers for intracellular and extracellular ions. Human serum albumin labeled with iodine-131 (I¹³¹) as a tracer was used in one patient to determine the volume of subarachnoid space.

Following the injections of the tracers, the researchers monitored the activity of the cerebrospinal fluid in the lateral ventricles and the lumbar subarachnoid space by assaying the radioactivity levels of the plasma for 5 hours. The investigators concluded that the amount of cerebrospinal fluid created daily is small and that fluid creation is not the sole responsibility of the choroid plexus, as was previously hypothesized. This study was supported by the National Institutes of Health, the U.S. Public Health Service, and the Associated Universities, Inc., and the U.S. Atomic Energy Commission.

References

Sweet, W.H., and H.B. Locksley. AFormation, Flow, and Reabsorption of Cerebrospinal Fluid in Man.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 84, No. 2, November 1953, pp. 397B402.  "

BNL-19. Study of Manganese Metabolism Using Manganese-56 as a Tracer

IN THE MID-1950s, researchers in the Medical Department of Brookhaven National Laboratory conducted a study to describe and determine the kinetics of the turnover of manganese-56 (Mn⁵⁶) in tissue, and to better understand the transport mechanisms directly from the bloodstream. Study subjects were 14 patientsC7 males and 7 femalesCbetween 40 and 71 years of age. Of these, six had Parkinson=s disease, three had metastatic cancer, two were hypertensive, one had heart disease, one had diabetes, and one had rheumatoid arthritis.

Between 15 and 20 microcuries of Mn⁵⁶, as the sulfate in saline solution, with 3.6 micrograms of stable Mn⁵⁶, were administered to each subject by intravenous injection following overnight fasting. Venous blood samples were obtained in quick succession after the administration, with the interval between samples increasing to 5 minutes. The samples were promptly assayed and weighed.

The study concluded that Mn⁵⁶ dispersed rapidly throughout the body, with the most rapid uptake occurring in the liver. From these data, the scientists concluded that mitochondrial uptake of manganese was the primary cause of the extensive retention and rapid tissue uptake. This study was supported by the U.S. Atomic Energy Commission.

References

Borg, D.C., and G.C. Cotzias. AManganese Metabolism in Man: Rapid Exchange of Mn⁵⁶ with Tissue as Demonstrated by Blood Clearance and Liver Uptake.@The Journal of Clinical Investigation. Vol. 37, No. 9, September 1958, pp. 1,269B1,278.  "

BNL-20. Experimental Systemic Therapy of Bone Tumors Using Gallium-72

BETWEEN 1954 AND 1958, the Medical Department of Brookhaven National Laboratory studied the effectiveness of gallium-72 (Ga⁷²) in therapy of bone cancers. Twenty-one patients were treated with Ga⁷² for advanced bone malignancies. Most of the patients had diffuse bone metastases secondary to breast or prostate cancer; the remainder had primary bone malignancies. All had exhausted conventional therapy before admission to Brookhaven National Laboratory Research Hospital.

The patients were intravenously injected with 1 microcurie of Ga⁷², in the form of gallium citrate, per kilogram of body weight. Complete blood and platelet counts were analyzed for damage to cells in the circulating blood and blood-forming tissues. Total-body doses of 75 rads or less were delivered, but the hematologic findings were similar to the effects seen with the administration of 150 to 200 rads of external x- or gamma radiation. The enhanced effect of the internal radiation exposure (compared to other patients receiving the same dose external to the body) was attributed to the localization of Ga⁷² in the bone.

The research also found that the effect of large doses of radiation on the bone marrow appeared to be cumulative to a point beyond which regeneration was not possible. It was also found that a total white count below 1,000 and a platelet count below 25,000 could be tolerated for weeks without infection or gross bleeding and with ultimate recovery. This study was supported by the U.S. Atomic Energy Commission.

References

Wolins, W., and V.P. Bond. AHematologic Findings in Human Beings Given Therapeutic Doses of Gallium-72.@Blood: The Journal of Hematology. Vol. 13, No. 9, September 1958, pp. 865B873.

Memorandum. L.E. Farr to file. September 18, 1953. Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.

Memorandum. C.G. Foster to Brookhaven National Laboratory Committee on Use of Radioactive Isotopes in Humans. July 19, 1954. Brookhaven National Laboratory Project H-34, Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.

Memorandum. E. Stickley to L.E. Farr and W. Wolins. August 20, 1954. Brookhaven National Laboratory Project H-34, Brookhaven National Laboratory, Clinical Research Center, Building 490, Human Medical Research Protocols.  "

BNL-21. Investigation of Carbohydrate Formation Using Carbon-14 B Labeled Acetate

BETWEEN 1956 AND 1957, the pathway of carbohydrate formation was investigated using carbon-14 (C¹⁴) by researchers at the Medical Department of Brookhaven National Laboratory. The study was conducted in two parts to include both diabetic and nondiabetic subjects.

In the first part, four patients hospitalized with various types of cancer were selected as the nondiabetic subjects. They included three males, aged 40 to 60 years, and one 63-year-old female. Subjects fasted 15 to 24 hours before being administered between 190 and 500 microcuries of C¹⁴-labeled sodium acetate by intravenous injection. Blood samples were obtained approximately 2 hours later and the blood sugar (glucose) was isolated and analyzed for the distribution of fatty acid carbons in the ring of the blood glucose.

In the second part, the diabetic group was composed of three females ages 11, 34, and 38 years, and two males ages 55 and 59 years. After fasting, they were administered 80 to 100 microcuries of C¹⁴-labeled acetate solution by intravenous injection. Similar analyses were performed to assess carbohydrate formation.

This study confirmed earlier findings and showed no differences in the formation of carbohydrates by normal and diabetic subjects. This work was supported by the U.S. Atomic Energy Commission.

References

Shreeve, W.W. APathways of Carbohydrates Formation in Man I. Isotope Distribution in Glucose from Nondiabetic Subjects Given 1-C¹⁴-Acetate.@The Journal of Clinical Investigation. Vol. 37, No. 7, July 1958, pp. 1,006B1,015.

Memorandum. W.W. Shreeve to the BNL Committee on the Use of Isotopes in Humans. February 12, 1957. Brookhaven National Laboratory Project H-38, Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-22. Studies on the Retention of Vitamin B Using Cobalt-60 and Cobalt-58 Tracers₁₂

FROM 1957 TO 1967, researchers at the Medical Research Center of Brookhaven National Laboratory conducted studies on the rate of loss of vitamin B₁₂ using cobalt-58 (Co⁵⁸) and cobalt-60 (Co⁶⁰) as tracers. The purpose of these studies was to evaluate the biological retention half-time of vitamin B₁₂ and to demonstrate its rate of loss from the body after administration of large amounts of the vitamin.

Ten clinic and hospital patients (males and females) with a variety of diagnosed blood diseases participated as study subjects. Each subject also received either an intravenous or an intramuscular injection of 0.3 to 3.0 microcuries ofCo⁶⁰-labeled vitamin B₁₂. Two subjects received intramuscular injections of 2 to 5 microcuries of Co⁵⁸-labeled hydroxocobalamin, a chemical analog of vitamin B₁₂. The first injection occurred in 1957. Six of the 10 subjects received nonradioactive cyanocobalamin or hydroxocobalamin therapy at varying intervals after the injection to their respective metabolism. Whole-body counting of patients administered radiocobalt-labeled vitamin B₁₂ began in early 1963 and continued through 1968.

This study showed that there is no single biological half-time for vitamin B₁₂ in man; rather, the biological half-time changes continuously over time. The study also showed that large dosages (500 to 1,000 micrograms) of vitamin B₁₂ or hydroxocobalamin caused a decrease in biological retention half-time, while small dosages of vitamin B₁₂ (100 micrograms) had no detectable effect on rate of loss. This work was supported by the U.S. Atomic Energy Commission.

References

Schiffer, L.M., S.H. Cohn, D.C. Price, and E.P. Cronkite. AWhole-Body Counting Studies of Retention and Accessibility of Radioactive Vitamin B₁₂.@The American Journal of Clinical Nutrition. Vol. 21, No. 6, June 6, 1968, pp. 665B672.  "

BNL-23. Use of Iodine-124 for Scanning Brain Tumors

THE APPLICABILITY OF iodine-124 as an imaging agent and tracer for certain proteins was investigated in a collaborative study between Brookhaven National Laboratory, the School of Medicine at Wake Forest University in North Carolina, and Massachusetts General Hospital. The study, which took place between 1958 and 1962, involved a combination of laboratory and clinical studies aimed at identifying the physiochemical properties and functions of serum proteins in cancer. The objective was to demonstrate that human fractionated globulin could be labeled with iodine-124 (I¹²⁴), and that such a preparation could be concentrated in sufficient amounts in brain tumor tissue to be detected by positron scanning.

The study group consisted of three patients with brain tumors that had been scanned previously with either radioactive copper or arsenic. Gamma globulin labeled with I¹²⁴ was injected and multiple scans were conducted to determine how effectively the labeled protein concentrated in tumors. A typical level of administered activity was 260 microcuries of I¹²⁴. Up to five scans were performed on each patient.

The experiment showed that I¹²⁴ could be used as an imaging agent for positron scanning, but the limited number of cases precluded any meaningful comparison with I¹³¹. The research was funded by the American Cancer Society and the U.S. Atomic Energy Commission.

References

Lippincott, S.W., C. Corcoran, C.R. Jensen, J.E. Jesseph, K. Rai, S. Aronow, M.W. Greene, and W.H. Sweet. ALabeling of Human Globulin with Iodine-124 for Positron Scanning of Neoplasms.@Journal of Nuclear Medicine. Vol. 5, 1964, pp. 193B199.  "

BNL-24. Studies of the Proliferation of Leukemic and Multiple Myeloma Cells Using Tritiated Thymidine

BETWEEN 1959 AND 1961, researchers at the Medical Research Center of Brookhaven National Laboratory conducted a series of studies to better understand the growth characteristics of normal and malignant (leukemia and multiple myeloma) cells. Thymidine labeled with tritium (H³) was used as a tracer of the biological process involved.

In one study, three patients with confirmed diagnoses of multiple myeloma participated as study subjects. There were two males and one female, ages 60, 69, and 44 years, respectively. Tritiated thymidine was administered to each subject in single intravenous injections. One subject received a second injection after an interval of 45 minutes. Bone marrow samples were obtained by aspiration from each subject 30 to 60 minutes after the injections. The samples were fixed and processed for examination by autoradiography. It was found that approximately 60 minutes after injection only about 3 percent of the myeloma cells were labeled. The generation time of the label ranged from 2 to 6 days.

The study of leukemic cells involved four subjects with various types of myelogenous leukemia. The subjects were two males and two females, aged 62, 65, 60, and 73 years, respectively. Tritiated thymidine was administered to each subject in a single intravenous injection. Samples of blood and one sample of bone marrow were obtained from each subject at intervals up to 24 hours after injection. The bone marrow samples were fixed and processed for examination by autoradiography.

This study showed that the average generation time for normal neutrophil precursors was approximately 48 hours. The researchers concluded that the study results did not support the general concept of acute leukemia as a disorder of rapid proliferation. This research was supported by the U.S. Atomic Energy Commission.

References

Killman, S.A., E.P. Cronkite, V.P. Bond, and T.M. Fliedner. AProliferation of Human Leukemic Cells Studied with Tritiated Thymidine In Vivo.@In Proceedings of the Eighth Congress of the European Society of Haemotology. Vienna, Austria, 1961.

Killman, S.A., E.P. Cronkite, T.M. Fliedner, and V.P. Bond. ACell Proliferation in Multiple Myeloma Studied with Tritiated Thymidine In Vivo.@Laboratory Investigation. Vol. 11, No. 10, October 1962, pp. 845B853.

Killman, S.A., E.P. Cronkite, J.S. Robertson, T.M. Fliedner, and V.P. Bond. AEstimation of Phases of the Life Cycle of Leukemic Cells from Labeling in Human Beings In Vivo with Tritiated Thymidine.@Laboratory Investigations. Vol. 12, No. 7, July 1963, pp. 671B684.  "

BNL-25. Study of the Role of Sodium in Hypertension Using Sodium-22

BETWEEN 1959 AND 1961, researchers at the Medical Research Center of Brookhaven National Laboratory studied the role of sodium in hypertension (high blood pressure). Subjects in the study were nine hypertensive patients, including seven males aged 48 to 66 years and two females aged 42 and 56 years; and nine normotensive (normal blood pressure) patients, including three males aged 39, 56, and 60 years, and six females aged 17 to 52 years. Some subjects were hospitalized for treatment of underlying diseases at the time of the study.

Between 2.6 and 7 microcuries of sodium-22 (Na²²) were administered orally with a low-sodium diet to each subject. Using a whole-body counter, the total-body retention of Na²² was measured in each subject at 1- to 3-day intervals for 6 to 11 months following administration.

Comparisons of the values obtained indicated that the biological retention half-time of Na²² was significantly longer in hypertensive subjects than in normotensive subjects, and that hypertensives may have a larger sodium pool than normotensives. This work was supported by the U.S. Atomic Energy Commission.

References

Dahl, L.K., M.G. Smilay, L. Silver, and S.C. Spraragen. AEvidence for a Prolonged Biological Half-Life of Na²² in Patients with Hypertension.@Circulation Research. Vol. 10, No. 3, March 1962, pp. 313B320.

Dahl, L.K., M.G. Smilay, L. Silver, and S.C. Spraragen. AProlonged Biological Half-Life of Sodium-22 in Patients with Essential Hypertension.@Nature. Vol. 192, No. 4799, October 21, 1961, pp. 267B268.

Smilay, M.G., L.K. Dahl, S.C. Spraragen, and L. Silver. AIsotopic Sodium Turnover Studies in Man: Evidence of Minimal Sodium (Na²²) Retention 6 to 11 Months After Administration.@The Journal of Laboratory and Clinical Medicine.Vol. 58, No. 1, July 1961, pp. 60B66.

Memorandum. L.K. Dahl and W.M. Gordon to the Committee for the Use of Isotopes in Humans. AUse of Na²² as a Tracer in Hospitalized Patients.@June 15, 1959. Brookhaven National Laboratory Project H-54, Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-26. Study of Iron Absorption and Loss by Whole-Body Counting Using Iron-59

DURING THE LATE 1950s AND EARLY 1960s, scientists at the Medical Research Center of Brookhaven National Laboratory, possibly in collaboration with researchers at Mount Sinai Hospital, New York, conducted a series of studies to better understand and to develop improved methods for evaluating iron metabolism in patients. Study subjects included patients with normal iron metabolism and/or patients under treatment for iron metabolism disorders due to underlying diseases. Some subjects participated in more than one study. Iron-59 (Fe⁵⁹) as ferrous citrate was administered to the subjects as a tracer of the biological processes of interest. Whole-body counting was also explored as a technique for determining the amount of iron retained in the body at different intervals after its intake.

Between 1959 and 1961, researchers at the Medical Research Center of Brookhaven National Laboratory conducted two related studies to determine and evaluate iron absorption, turnover, and loss as measured by whole-body counting using Fe⁵⁹ tracer. Fifty female patients participated as study subjects in one of the two studies, including 14 with polycythemia vera (malignant overproduction of red cells), 6 with longstanding menorrhagia (excessive menstrual bleeding), 4 with aplastic anemia, 10 with various chronic nonmalignant conditions, and 16 patients whose iron metabolism was normal. Approximately 40 of these subjects also participated in a follow-up study.

In both studies, 1 to 10 microcuries of Fe⁵⁹ as ferrous citrate were administered orally to each subject, followed by a drink of water. No food was given for 1 hour. Several 2- to 10-minute body counts were obtained for each subject over the 8- to 10-hour period following the ingestion of Fe⁵⁹ to determine body Fe⁵⁹ content. Whole-body counts were also obtained at intervals over periods up to several months to measure Fe⁵⁹ retention and subsequent loss. These studies demonstrated the benefits of using Fe⁵⁹ with whole-body counting in studying iron metabolism. This research was supported by the U.S. Atomic Energy Commission.

References

Price, D.C., S.H. Cohn, E.P. Cronkite, L. Wasserman, and P. Reizenstein. AWhole-Body Counter Studies of the Absorption and Turnover of Iron and Vitamin B₁₂.@In Proceedings of the English Congress of the European Society of Haematology. Vienna, Austria, 1961.

Price, D.C., S. H. Cohn, E.P. Cronkite, L. Wasserman, and P. Reizenstein. AThe Determination of Iron Absorption and Loss by Whole-Body Counting.@Blood: The Journal of Hematology. Vol. 20, No. 5, November 1962, pp. 517B531.

Price, D.C., S.H. Cohn, and E.P. Cronkite. AAbsorption and Turnover Rates of Iron Measured by the Whole-Body Counter.@In Radioactivity in Man, edited by Meneely, G.R., and S.M. Linde. Springfield, IL: Charles C. Thomas, pp. 370B390.

Schiffer, L.M., D.C. Price, J. Cuttner, S.H. Cohn, and E.P. Cronkite. AA Note Concerning the >100 Percent Value=in Iron Absorption Studies by Whole-Body Counting.@Blood: The Journal of Hematology. Vol. 23, No. 6, June 1964, pp. 757B761.  "

BNL-27. Plasma Binding Capacity for Vitamin B₁₂Using Cobalt-57 Tracer

DURING THE EARLY 1960s, researchers at Brookhaven National Laboratory and the Long Island Jewish Hospital in New York conducted studies on the plasma binding capacity for vitamin B₁₂ (cyancobalamin) using cobalt-57 (Co⁵⁷) as an isotope label. Subjects included four hospitalized patients with normal serum vitamin B₁₂ levels, and four patients with known pernicious anemia in remission who were receiving routine monthly therapeutic injections of vitamin B₁₂. Three subjects received an intravenous injection and five subjects received an intramuscular injection of 2.5 to 5.0 microcuries of Co⁵⁷-labeled vitamin B₁₂. Blood samples were drawn at various intervals over a 48-hour period and the Co⁵⁷ activity was measured in the separated plasma. Total plasma vitamin B₁₂ volume was calculated.

These studies provided new information about the plasma binding capacity for vitamin B₁₂, and demonstrated the presence of protein carriers involved in vitamin B₁₂ transport in plasma. This work was supported by the U.S. Atomic Energy Commission.

References

Schiffer, L.M., E.P. Cronkite, L.M. Meyer, and I.F. Miller. AIn Vivo Plasma Binding Capacity for Cyanocobalamin.@British Journal of Haematology. Vol. 12, No. 5, September 1966, pp. 578B582.  "

BNL-28. A Short-Term Comparison of Calcium and Strontium Metabolism Using Calcium-47 and Strontium-85

DURING THE EARLY 1960s, scientists at Brookhaven National Laboratory compared the behavior of strontium and calcium using calcium-47 (Ca⁴⁷) and strontium-85 (Sr⁸⁵). Study subjects were six patients (four females and two males) between the ages of 30 and 73 years, with different clinical conditions reflecting various degrees of skeletal involvements.

Subjects were administered 20 microcuries of Ca⁴⁷ and 5 microcuries of Sr⁸⁵ intravenously in the form of their chloride salts. Blood samples were collected at 4, 12, and 24 hours and on days 2, 3, 4, 5, 7, and 10 after injection. Twenty-four hour urine and stool samples were collected from each patient for 10 days after administration of the isotope. The concentrations of Ca⁴⁷ and Sr⁸⁵ were measured in the excreta and blood samples. Body retention was determined by whole-body counting daily for the first 10 days, then every second day for the next 20 days.

This study showed no differences between the rates at which the skeleton absorbs Ca⁴⁷ and Sr⁸⁵ during the first 10-day period. However, differences between the rates developed subsequently, and Ca⁴⁷ and Sr⁸⁵ metabolism over the long term could not be predicted from data obtained within 10 days of administration. This work was supported by the U.S. Atomic Energy Commission.

References

Cohn, S.F., S.W. Lippincott, E.A. Gusmano, and J.S. Robertson. AComparative Kinetics of Calcium-47 and Strontium-85 in Man.@Radiation Research. Vol. 19, No. 1, 1963, pp. 104B119.  "

BNL-29. Study of Tryptophan Metabolism Using Carbon-14

IN THE EARLY 1960s, researchers at Brookhaven National Laboratory examined the effects on tryptophan metabolism in humans of the administration of tryptophan-2 labeled with carbon-14 (C¹⁴) with and without unlabeled tryptophan carrier. Loading studies were conducted to allow the detection of abnormal metabolism which might not have been detected otherwise. Study subjects were six volunteer patients ranging in age from 45 to 72 years; three males (two whites and one black) and three females. They were hospitalized on the metabolic ward with achondroplasia with osteoarthritis (one subject), alcoholism with gallstones (one subject), multiple myeloma (three subjects), and breast cancer (one subject).

Under controlled dietary and drug conditions, each patient was administered 17 to 78 milligrams of DL-tryptophan-2 with 96 to 157 microcuries of C¹⁴ as a tracer. All doses were administered orally except for one intravenous injection of DL-tryptophan-2-C¹⁴.

Samples of expired air, urine collected for four consecutive 24-hour periods (one before and three after administration), and blood were obtained from each patient. These samples were then analyzed for C¹⁴ activity from labeled carbon dioxide (C¹⁴O₂) and tryptophan metabolites relative to standard (control) values. About 19 to 36 percent of the total C¹⁴ administered was excreted in the urine, with or without the loading dose of unlabeled tryptophan. This study was supported in part by the American Cancer Society, the National Cancer Institute, and the U.S. Atomic Energy Commission.

References

Hankes, L., R. Brown, S. Lippincott, and M. Schmaeler. AEffects of L-tryptophan Load on the Metabolism of Tryptophan-2-C¹⁴ in Man.@Journal of Laboratory and Clinical Medicine. Vol. 69, 1967, pp. 313B324.  "

BNL-30. Use of Iodine-131 and Tritium Tracers in Studies of Vasopressin Metabolism

IN 1960, researchers at the Medical Research Center of Brookhaven National Laboratory studied the usefulness of iodine-131 (I¹³¹) and tritium (H³) as radioactive labels on vasopressin in studies of vasopressin metabolism in humans under various physiological and clinical conditions. Vasopressin, which was isolated from beef pituitary glands, is an antidiuretic hormone.

Five ambulatory hospital patients were selected for this study. They included patients with both normal and elevated blood pressures. Two subjects were given arginine vasopressin (AGV) labeled with I¹³¹ (approximately 0.8 microcurie); another subject was given AGV labeled with tritium (6.25 or 12.5 microcuries); the remaining two subjects were given labeled forms of AGV. Blood samples were drawn at intervals up to 3 hours after injection and the levels of I¹³¹ and H³ in the plasma were measured. The results showed that I¹³¹ and tritium were effective labels for studying vasopressin metabolism under various conditions. This work was supported by the U.S. Atomic Energy Commission.

References

Silver, L., I. Schwartz, C.T.O. Fong, A.F. Debons, and L.K. Dahl. ADisappearance of Plasma Radioactivity after Injection of H³ or I¹³¹­Labeled Arginine Vasopressin.@Journal of Applied Physiology. Vol. 16, No. 6, November 1961, pp. 1,097B1,099.  "

BNL-31. Metabolism of Carbon-14 B Labeled Acetate in Diabetics

IN 1960, a study was conducted at the Medical Research Center of Brookhaven National Laboratory to learn more about the metabolism of acetate in diabetics. Four subjectsCtwo with juvenile-type diabetes in severe ketoacidosis (a condition resulting from severe insulin deficiency) and two with stable adult-type diabetes and mild ketosisCwere included in the study.

None of the patients received insulin within 24 hours of the experiment and none received long-acting insulin within 72 hours. The stable diabetic subjects received 30 milligrams of prednisone 3 and 9 hours prior to injection of acetate. Subjects then received 50 to 100 microcuries of sodium acetate labeled with carbon-14 (C¹⁴) by intravenous injection.

Blood samples were collected at later time intervals for analyses for C¹⁴-ketone bodies and C¹⁴-glucose (blood sugar). Urine samples were collected at 2 and 6 hours for analysis for C¹⁴ in ketone bodies and glucose. The breath of the stable diabetics was sampled at intervals for C¹⁴­labeled carbon dioxide. This study showed that ketone bodies in diabetes are not part of the metabolic process that converts acetate to carbon dioxide. The study was funded by the U.S. Atomic Energy Commission.

References

Shreeve, W.W., and P.M. Tocci. AConversion of 1-C¹⁴-Acetate to Ketone Bodies in Diabetics.@Metabolism. Vol. 10, No. 7, 1961, pp. 522B534.

Memorandum. W.W. Shreeve to the Committee for the Use of Isotopes in Humans. December 20, 1955. Brookhaven National Laboratory Project H-41, Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-32. Study of Vitamin B₁₂Metabolism Using Cobalt-58 and Cobalt-60

IN 1960 AND 1961, researchers at the Medical Research Center of Brookhaven National Laboratory studied the metabolism of vitamin B₁₂ after administration by different routes, to determine the effect of the administration route. Four hospital patients with illnesses unrelated to vitamin B₁₂ metabolism participated as subjects.

Two patients were given double tracers of 2 microcuries of cobalt-60 (Co⁶⁰)Blabeled vitamin B₁₂ administered by intravenous injection, followed 3, 4, and 7 days later by oral administrations of 3.56 microcuries of cobalt-58 (Co⁵⁸)Blabeled vitamin B₁₂. Cobalt-58 and Co⁶⁰ radioactivity retained by these subjects was measured at intervals for up to 60 days.

Two other subjects first were given 20 microcuries per 0.21 micrograms of Co⁵⁸-labeled vitamin B₁₂ orally followed after 30 and 42 days, respectively, by intravenous administration of 15 microcuries per 0.20 micrograms of Co⁵⁸-labeled vitamin B₁₂. Plasma radioactivity levels were measured for another 35 and 48 days, respectively. Whole-body turnover rates of ingested and injected vitamin B₁₂ were measured over 250 days.

The results indicated there was little difference between the excretion rates of orally and intravenously administered vitamin B₁₂. The research was supported by the U.S. Atomic Energy Commission.

References

Reizenstein, P., E.P. Cronkite, and S.A. Cohn. APlasma Clearances and Whole-Body Turnover of Injected and Absorbed Radioactive Vitamin B₁₂ in Man.@The Journal of Laboratory and Clinical Medicine. Vol. 62, No. 2, August 1963, pp. 255B262.

Reizenstein, P., E.P. Cronkite, and J.S. Robertson. ARelations of the Turnover of Tracer Vitamin B₁₂ to that of Unlabeled B₁₂ in the Body Stores.@In Proceedings of the Second European Symposium on Vitamin B₁₂ and Intrinsic Factor. Hamburg, Germany, 1961.

Memoranda. P.G. Reizenstein to the Committee on Use of Radioactive Isotopes in Patients. June 17, 1960 and October 20, 1960. Brookhaven National Laboratory Project H-63, Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-33. Studies of Strontium Metabolism Using Calcium-47 and Strontium­85

BETWEEN 1960 AND 1962, researchers at the Medical Research Center of Brookhaven National Laboratory conducted a series of studies to characterize the short- and long-term metabolism of strontium in the human body and to compare it with that of calcium. Strontium-85 (Sr⁸⁵) and calcium-47 (Ca⁴⁷) were used as tracers of the biological processes involved in subjects with either bone disease or normal calcium balances.

Long-term biological turnover of Sr⁸⁵ was studied among 10 subjects; 6 males ranging in age from 54 to 73 years, and 4 females, ages 57 to 73 years. All 10 subjects were ambulatory patients in good physical condition, but had primary diagnosis of nonmetastatic cancer with 10 to 13 years survival after surgery for: cancer of the breast (2 subjects) or thyroid (1 subject); thyroid cancer, status unspecified (1 subject); pseudomyxoma peritonei (mucuslike material in the abdominal cavity) with diabetes (1 subject); hypopituitarism secondary to a pituitary tumor (1 subject); Paget=s disease of bone (1 subject); and osteoporosis, alone or with osteoarthritis (3 subjects). Of these, eight subjects had associated skeletal disease, but six had normal calcium balances and possibly served as comparison subjects.

Single intravenous injections of 10 to 14 microcuries of Sr⁸⁵ were administered to eight subjects. Forty microcuries Sr⁸⁵ were administered orally to each of the other two subjects. Urine and feces were collected for 24-hour periods for 20 to 48 days after the Sr⁸⁵ administrations and were analyzed for Sr⁸⁵. Urinary excretion of calcium was measured daily for each subject. Whole-body retention of Sr⁸⁵ was measured weekly in the whole-body counter. Based on 100 to 320 days of observation, the biological retention half-time of strontium was estimated to be 843 days. Data were insufficient to distinguish between two mathematical models developed to describe the life-time biological turnover of Sr⁸⁵ in humans.

In a related study, the same researchers examined the effects of prolonged daily ingestion of stable strontium on the long-term turnover of strontium fixed in bone. Four female patients participated as subjects, including three who participated in the long-term Sr⁸⁵ turnover study (above). Ten microcuries of Sr⁸⁵ were administered intravenously to each subject. From 130 to 240 days after Sr⁸⁵ administration, the subjects were given daily dietary supplements of 1,100 grams of calcium gluconate (two subjects) or 570 grams strontium lactate (two subjects).

The Sr⁸⁵ turnover rates determined for this period were found not to be statistically different from the pre-Sr⁸⁵ administration, suggesting that the exchange of bone-fixed strontium is not influenced directly by the amount of stable strontium or calcium available for exchange.

Subsequently, the research team conducted a further study to compare the short-term kinetics of Ca⁴⁷ and Sr⁸⁵ in humans. Six patientsCtwo males aged 30 and 56 years, respectively, and four females between the ages of 53 and 73 years (none of whom was included in the long-term kinetic studies)Cparticipated as subjects. Of these, three had multiple myeloma, and the three others had essential hypertension, scleroderma, and chylous ascites (serous fluid in the abdominal cavity, Adropsy@), respectively. Their degrees of disease-related skeletal involvement ranged from Anormal@(one subject) to Aextensive@(one subject).

A moderately alkaline saline solution of 2 microcuries of high-specific-activity Ca⁴⁷ chloride and 5 microcuries of Sr⁸⁵ chloride tracers was administered by intravenous injection. Blood samples were collected at 4, 12, and 24 hours, and on days 2, 3, 5, 7, and 10 after administration of the radionuclides. Daily urine and stool samples were collected from each patient during the same period. Plasma, urine, and stool samples were measured for radioactivity. Whole-body retention of Sr⁸⁵ was measured by gamma spectrometry, daily for the first 10 days, and twice weekly for the next 20 days.

The results indicated that similarities observed between strontium and calcium metabolism in the short term (10 days) are not predictive of their kinetics in the long term. This work was supported by the U.S. Atomic Energy Commission.

References

Cohn, S., H. Spencer, J. Samachuson, A. Felstein, and E. Gusmano. AInfluence of Dietary Stable Strontium and Calcium on the Turnover of Bone-Fixed Sr⁸⁵ in Man.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 110, 1962, pp. 526B528.

Cohn, S., H. Spencer, J. Samachuson, and J. Robertson. AThe Turnover of Strontium-85 in Man as Determined by Whole-Body Counting.@Radiation Research. Vol. 17, No. 2, August 1962, pp. 173B185.

Cohn, S.H., S.W. Lippincott, E. Gusmano, and J. Robertson. AComparative Kinetics of Calcium-47 and Strontium-85 in Man.@Radiation Research. Vol. 19, 1963, pp. 104B119.

Robertson, J.S., and S. Cohn. AUse of an Analog Computer in Studies of Strontium and Calcium Metabolism in Man.@Annals of the New York Academy of Sciences. Vol. 108, Art. 1, May 10, 1963, pp. 122B127. "

BNL-34. Study of the Metabolism of Cesium-137

BETWEEN 1960 AND 1962, researchers in the Metabolic Section of the Veterans Administration Hospital, Hines, Illinois, and the Medical Research Center of Brookhaven National Laboratory collaborated on a study of cesium-137 (Cs¹³⁷) metabolism in humans. A total of 15 hospitalized patients participated in the study.

Eleven of the 15 subjects reportedly had good nutrition, normal kidney function, and healthy gastrointestinal tracts. Nine of the subjects were males, ages 45 to 66 years, 7 of whom had malignant diseases including Hodgkin=s disease (2 subjects); lung cancer (3 subjects); multiple myeloma (1 subject) and lymphoma (1 subject); and 2 had chronic lung diseases. The other six subjects were females, ages 48 to 66 years, with cancers of the colon (two subjects), breast (two subjects), or uterus (one subject), or Hodgkin=s disease (one subject).

Single administrations of between 10 and 50 microcuries of Cs¹³⁷ chloride were given by intravenous injection to eight subjects, and orally to the other seven subjects. Cesium-137 activity was measured in samples of blood, urine, and feces obtained from 11 of the subjects at intervals over periods ranging from 9 up to 160 days after the Cs¹³⁷ administration. Five subjects also had whole-body counts about three times a month. The distribution of Cs¹³⁷ was also studied in tissues obtained from five of the subjects after their deaths from their disease which occurred 3 to 165 days after the Cs¹³⁷ administration.

The investigators found that Cs¹³⁷ taken orally was rapidly and almost completely absorbed into the bloodstream where it was cleared quickly and deposited preferentially in muscle. The major route of excretion was found to be through the kidney into the urine. Estimation of the biological half-time for cesium by analysis of excreta (two subjects) was found to be 50 and 60 days, respectively. Estimates of biological retention half-time by whole-body counting ranged from 54 to 114 days with an average of 75 days. This research was supported by the U.S. Atomic Energy Commission. 

References

Cohn, S.H., B. Rosoff, and H. Spencer. AI. Cesium-137 Metabolism in Man.@Radiation Research. Vol. 19, No. 4, August 1963, pp. 643B654.

Cohn, S.H., B. Rosoff, E.A. Gusmano, and H. Spencer. AII. Long Term Cs¹³⁷ Turnover in Man as Measured by a Whole-Body Counter.@Radiation Research. Vol. 19, No. 4, August 1963, pp. 655B658.  "

BNL-35. Study of Tryptophan Conversion to O-Aminophenol Using Carbon­14

A STUDY IN 1961 by researchers at Brookhaven National Laboratory determined that tryptophan (an essential amino acid), was metabolized to o-aminophenol, a urinary product of tryptophan. This process was shown using carbon-14 (C¹⁴) as a tracer.

Thirty-nine milligrams of DL-tryptophan-7a-C¹⁴ containing 51 microcuries of C¹⁴ were administered orally to one female patient with multiple myeloma. Expired carbon dioxide (CO₂) and urinary output were collected for the next 12 to 24 hours, respectively. Of the administered C¹⁴, 5 percent was found to have been excreted as expired C¹⁴O₂ in 12 hours, and 14 percent was excreted in the urine in 24 hours. The metabolite o-aminophenol-2-C¹⁴ was identified in the urine. The study was supported by the U.S. Atomic Energy Commission.

References

Hankes, L., M. Schmaeler, and K. Rai. AO-aminophenol: A Urinary Product of Tryptophan Metabolism in the Human.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 110, 1962, pp. 420B422.  "

BNL-36. Total-Body Water and Hematologic Studies in the Pacific Islanders Using Chromium-51 and Tritium

BETWEEN 1961 AND 1966, a medical team from Brookhaven National Laboratory conducted a series of studies on persons, both natives and others, living in the Marshall Islands. These islands and some of the population were contaminated with radioactive fallout as the result of an unexpected distribution of fallout from a nuclear test on Bikini Atoll in 1954.

In 1961, five Marshallese and five Americans were administered chromium-51 (Cr⁵¹)Blabeled red cells by intravenous injection to determine their blood volumes. In 1962, eight unexposed Rongelap Island natives and seven Americans participated in an identical procedure. Another group of 25 subjects may have undergone the same study during the period 1961 to 1962.

In 1963, 21 Marshallese islanders were administered Cr⁵¹ and 1 milliliter of water labeled with tritium (H³) to determine red cell mass, blood volume, lean body mass, and total-body water. Similar body-water and lean-body-mass studies were conducted on residents of Enewetok Atoll in 1965 and 1966.

These studies showed that there was a slight tendency for the Marshallese to be anemic. It was determined that the anemia was characteristic of the Pacific island study population and not the result of exposure to fallout radiation. This work was supported by the U.S. Atomic Energy Commission.

References

Conard, R., L. Meyer, W. Sutow, W. Maloney, B. Cannon, A. Hicking, R. Hammerstrom, E. Riklon, A. Lowery, A. Wathe, R. Carter, B. Bender, I. Lanwi, and J. Anjain. Medical Survey of People of Rongelap and Utirik Islands Nine and Ten Years after Exposure to Fallout Radiation (March 1963 and March 1964). Upton, NY: Brookhaven National Laboratory, BNL-908, pp. 39B40.

Correspondence. L. Meyer and W. Siri. Lawrence Berkeley Laboratory, William E. Siri Files, Accession 434-91-0131, File Code 19-14-18, Carton 119.  "

BNL-37. Study of Iron Metabolism in Humans with Aregenerative Anemia Using Iron-59 and Chromium-51

IN APPROXIMATELY 1962, researchers at the Medical Research Center of Brookhaven National Laboratory conducted a study to better understand the effect of anemia (low red blood-cell count) on iron metabolism in humans. This study involved four male and three female patients, ranging in age from 5 to 68 years, who had aregenerative anemia (reduced capacity to replace red blood cells), and two normal subjects. Subsequently, the Brookhaven researchers collaborated with medical scientists at the Karolinska Hospital in Stockholm, Sweden, to increase the size of the study group. Twenty anemia patients and 37 others of unspecified health status participated in the collaborative Swedish-American study.

Subjects initially were orally administered 250 micrograms of iron as ferrous sulfate or gluconate together with 0.5 to 5.0 microcuries of iron-59 (Fe⁵⁹) as a tracer to evaluate iron absorption and excretion. At Brookhaven, red blood-cell mass was measured in patients using a standard test involving administration of chromium-51 (Cr⁵¹). On completion of the absorption study, all patients received 1 to 10 microcuries of Fe⁵⁹ as ferrous citrate by intravenous injection for other evaluations.

From the results of these studies, it was concluded that anemia has an effect on iron absorption; however, the relationship was not well defined. The initial study was supported solely by the U.S. Atomic Energy Commission. The second study in this series was supported jointly by the Swedish Nutritional Foundation, the O. and E. Ericsson Foundation, and the U.S. Atomic Energy Commission.

References

Schiffer, L.M., D.C. Price, and E.P. Cronkite. AIron Absorption and Anemia.@The Journal of Laboratory and Clinical Medicine. Vol. 65, No. 2, February 1965, pp. 316B321.

Schiffer, L.M., I. Brann, E.P. Cronkite, and P. Reizenstein. AIron Absorption and Excretion in Aregenerative Anaemia: A Collaborative Swedish-American Whole-Body Counter Study.@Acta Haematologica. Vol. 35, 1966, pp. 80B90.  "

BNL-38. Metabolism of Zinc-65

IN 1962 AND 1963, researchers in the Metabolic Section of the Veterans Administration Hospital, Hines, Illinois, and the Medical Research Center of Brookhaven National Laboratory, investigated the metabolism of zinc-65 (Zn⁶⁵). A total of 19 hospitalized patients participated as study subjects, including 4 males ranging in age from 56 to 73 years and 4 females ranging in age from 45 to 60 years. Subjects had been diagnosed with cancer of the breast (three female subjects); lung (two subjects) or larynx (one subject); rheumatoid arthritis (one subject); or chronic pulmonary disease. These subjects were well-nourished, had normal kidney function and disease-free gastrointestinal tracts, and received 10 to 12 milligrams of stable zinc in their daily diet.

Tracer amounts (20 to 53 microcuries) of Zn⁶⁵ as chloride were administered to each subject in single intravenous injections. Serial blood samples were obtained with declining frequency after the first day following the Zn⁶⁵ administration throughout the study period. Zinc-65 activity in these samples and in 24-hour urine samples and all fecal samples was determined throughout the study. Retention of Zn⁶⁵ was estimated in two subjects by whole-body counting.

Eleven subjects participated in the tissue distribution phase of this study. These subjects, including seven males ranging in age from 56 to 90 years and four females ranging in age from 32 to 67 years, had advanced malignant diseases of various types, including: bronchogenic cancer (three subjects); cancers of the colon (two subjects), breast (one subject), pancreas with ascites (one subject); Hodgkin=s disease (one subject); fibrosarcoma with bone involvement; and hepatoma (liver tumor) (one subject). Each subject received 100 microcuries of Zn⁶⁵ with 0.001 to 2.0 milligrams of stable zinc chloride in a single intravenous injection. Samples of blood, urine, feces, and solid tissues were obtained for radioassay at autopsy, 1 to 71 days after the Zn⁶⁵ administration.

The study found that Zn⁶⁵ levels in blood decreased rapidly while concentrations in whole blood (most notably red blood cells) remained high. Zinc-65 uptake was found to be highest in the liver, spleen, and kidney, followed by glandular organs, such as the pancreas and prostate gland. This work was supported by the National Cancer Institute and the U.S. Atomic Energy Commission.

References

Rosoff, B., F. Stand, and H. Spencer. ATissue Distribution of Zn⁶⁵ in Man.@In Federation Proceedings. Vol. 22, No. 2, 1963.

Spencer, H., B. Rosoff, A. Feldstein, S.H. Cohn, and E. Gusmano. AMetabolism of Zinc-65 in Man.@Radioactive Research. Vol. 24, No. 3, March 1965, pp. 432B445.   "

BNL-39. Study of Fatty Acid Synthesis Using Tritium and Carbon-14 Labeled Glucose and Lactic Acid B

BETWEEN 1962 AND 1964, investigators at the Medical Research Center of Brookhaven National Laboratory and the Department of Physiology, University of Cincinnati School of Medicine, collaboratively conducted a study to examine the relative efficiency of glucose and lactic acid as sources of hydrogen in fatty acid synthesis, using tritium (H³) and carbon-14 (C¹⁴) as tracers. Study subjects included lean diabetics, obese mild diabetics, and obese nondiabetics who had fasted overnight.

Subjects received H³-labeled and C¹⁴-labeled glucose or similarly labeled lactic acid by intravenous injection. Blood samples were drawn at various intervals after the injection, and the H³ and C¹⁴ activity in the plasma triglycerides (fatty acids) and plasma water and the concentration of plasma triglycerides were determined.

The study showed that triglyceride fatty acid synthesis did not depend solely on glucose; the availability of other hydrogen sources, such as the oxidation of lactic acid, was even more important. This study was supported by the U.S. Atomic Energy Commission.

References

Ghose, A., W.W. Shreeve, Y. Shigeta, and I.L. Schwartz. AIncorporation of Tritium into Human Plasma Triglycerides from Glucose-I-H³ and Lactic Acid-2-H³.@Nature. Vol. 201, No. 4920, February 15, 1964, pp. 722B723.

Memorandum. W.W. Shreeve to Brookhaven National Laboratory Committee on Use of Radioactive Isotopes in Human Studies. November 1, 1961. Brookhaven National Laboratory Project H-72, Brookhaven National Laboratory, Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-40. Study of the Metabolism of a Bladder Carcinogen Using Carbon-14

IN APPROXIMATELY 1963, Brookhaven National Laboratory researchers conducted a study of the metabolism of 3-hydroxyanthranilic acid using carbon-14 (C¹⁴) as a tracer. Three-hydroxyanthranilic acid is a metabolite of tryptophan that at the time of the study had been confirmed as a bladder carcinogen in mice, and had been observed in abnormally high levels in patients with bladder cancer.

Fourteen milligrams of carboxyl-labeled 3-hydroxyanthranilic acid containing 51 microcuries of C¹⁴ were administered orally to a 51-year-old female subject with achondroplasia (abnormal conversion of cartilage into bone).

Twenty-four-hour collections of expired carbon dioxide and urine, and blood samples drawn at 0, 0.5, 2, 4, 8, 12, and 24 hours after the administration, were analyzed for C¹⁴ activity. Within 6 hours, 40 percent of the administered activity appeared in expired air as C¹⁴O₂; 35 percent and another significant amount of activity were found in the urine and circulating blood, respectively, within 24 hours. This study was supported by the U.S. Atomic Energy Commission and in part by the American Cancer Society, the National Cancer Society, and the National Cancer Institute.

References

Hankes, L., R. Brown, M. Schmaeler, and S. Lippincott. AMetabolism of 3-Hydroxyanthranilic Acid-Carboxyl-C¹⁴ in the Human.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 115, 1964, pp. 1,083B1,088.  "

BNL-41. Study of Metabolism of Lactate and Pyruvate with Diabetes Using Carbon-14 Tracer

IN 1963, RESEARCHERS at the Medical Research Center of Brookhaven National Laboratory conducted a series of 17 studies of the effects of diabetes, insulin, tolbutamide (an anti-diabetic medication), and glucose on the metabolism of carbon-14 (C¹⁴)Blabeled lactic and pyruvatic acids. The study subjects included four patients (two males and two females, ages 32 to 60 years) with diabetes of varied severity. Two other subjects, females ages 32 and 37 years, were nondiabetics.

All subjects were administered 50 microcuries of C¹⁴-labeled lactate or C¹⁴-labeled pyruvate in 10 to 25 milliliters of normal saline by intravenous injection. Insulin in an amount proportional to body weight was either injected 5 to 10 minutes before intravenous injection of the C¹⁴-labeled lactate or pyruvate, or infused 30 to 45 minutes prior to, and 45 to 60 minutes after injection of the labeled compound. Twenty-five grams of glucose were injected 20 minutes before injection of the C¹⁴-labeled compound. Tolbutamide was administered 15 to 20 minutes before the labeled compound.

Breath samples were collected 15, 30, 45, 60, 90, 120, 180, and 240 minutes after injection of the labeled compounds and measurements were made of carbon dioxide exhaled by the subjects. Blood samples were also obtained to measure the concentration of C¹⁴-labeled lactate and pyruvate in the blood.

This study showed that the insulin does not promote the utilization of lactic acid compared to its effect on the utilization of glucose. This work was funded by the U.S. Atomic Energy Commission.

References

Shreeve, W.W., R.C. DeMeutter, and Y. Shigeta. ADiabetes, Insulin, Tolbutamide, and Glucose Load in the Degradation of C¹⁴-Labeled Lactate and Pyruvate.@The Journal of the American Diabetes Association. Vol. 13, No. 6, NovemberBDecember 1964, pp. 615B621.  "

BNL-42. A Study of Calcium Metabolism in Parathyroid Deficiency Using Tracer Calcium-47

IN 1963,RESEARCHERS in the Medical Research Center of Brookhaven National Laboratory investigated the effects of parathyroid hormone deficiency on calcium metabolism. Calcium-47 (Ca⁴⁷) was used as tracer in the study of calcium metabolism in a 64-year-old female patient with hypoparathyroidism (decreased function of the parathyroid glands) following an operation for a goiter (disease of the thyroid gland) approximately 6 years previous. Hypoparathyroidism is associated with low levels of parathyroid hormone and is characterized by low levels of calcium in the blood and neurologic disorders.

The control group consisted of two males, 79 and 80 years old, with normal calcium metabolism.

The patient and normal control subjects were fed a normal diet with controlled levels of calcium and phosphorus for 10 days prior to receiving the Ca⁴⁷ tracer. Each subject in the study received 20 microcuries of Ca⁴⁷ administered intravenously as calcium chloride. The levels of Ca⁴⁷ were measured daily in the blood, urine, and feces for 10 days. Retention of Ca⁴⁷ in the body was measured with whole-body counts at Brookhaven.

This study provided information that was used to formulate a computer model of calcium biokinetics in the body. This study was funded by the U.S. Atomic Energy Commission.

References

Cohn, S.H., S. Bozzo, N. Glatstein, C. Constantinides, J. Litvak, and E.A. Gusmano. AFormulation of a Compartmental Model in the Study of Partial Parathyroid Deficiency.@Metabolism. Vol. 13, No. 11, 1964, pp. 1,356B1,368.  "

BNL-43. The Study of Menstruation and Resulting Iron Deficiency Using Whole-Body Counting

IN 1963,SCIENTISTS at the Medical Research Center of Brookhaven National Laboratory studied iron absorption among nine women with various menstrual histories, including six parous (borne children) women with histories of heavy menses and related hypochromic anemia (abnormally low hemoglobin content in red cells), and one nulliparous (not borne a child) unmarried woman with normal menses and a normal blood count. A post-menopausal patient with marked iron-deficiency due to phlebotomy (bloodletting) treatment for polycythemia vera (a malignant excess of red blood cells), but no blood loss during the study period, served as a comparison subject.

One to 10 microcuries of iron-59 (Fe⁵⁹) in 250 micrograms of carrier (stable) iron were administered orally to each subject following an overnight fast. Serial body counts were obtained over the subsequent 4 to 10 hours to establish each subject=s Fe⁵⁹ activity level. Each patient=s hemoglobin, microhematocrit, red blood-cell count, and red cell indices were determined on the day of Fe⁵⁹ administration, together with plasma iron and unsaturated iron-building capacities. Between days 10 and 30, several blood samples were obtained from each patient and measured for Fe⁵⁹ level.

The results of this study showed that menstrual blood loss in women with excessive bleeding was 110 to 550 milliliters, whereas normal women lost only 33 to 59 milliliters of blood during menstruation. The heavily menstruating women were found to have much greater iron absorption compared to normal women. This research was supported by the U.S. Atomic Energy Commission.

References

Price, D.C., E.M. Forsyth, S.H. Cohn, and E.P. Cronkite. AThe Study of Menstrual and Other Blood Loss, and Consequent Iron Deficiency, by Fe⁵⁹ Whole-Body Counting.@The Canadian Medical Association Journal. Vol. 90, Jan. 11, 1964, pp. 51B54.  "

BNL-44. Characterizing Gamma Globulin Levels in Multiple Sclerosis with Iodine-131

IN 1964, researchers from the Medical Department of Brookhaven National Laboratory in cooperation with scientists from medical departments at Bowman Gray School of Medicine of Wake Forest University, North Carolina; the University of California, Los Angeles; and the Jewish Chronic Diseases Hospital, New York conducted a study involving 21 patients with established cases of multiple sclerosis. The objective of this study was to determine the level of gamma globulin in the blood and cerebrospinal (brain and spinal cord) fluid and the exchange rate between the two. Male and female hospitalized patients between 29 and 66 years of age, who had been symptomatic from 5 to 25 years, were studied.

Gamma globulin obtained from normal donor serum was labeled with iodine-131 (I¹³¹), using an established technique. Between 0.5 and 2.0 milligrams of I¹³¹-labeled gamma globulin with 15 to 150 microcuries of I¹³¹ were administered intrathecally (through the covering of the spinal cord into the space between it and the spinal cord) to all the patients.

After the required samples of cerebrospinal fluid and blood were obtained, at least two of the same patients and four other multiple sclerosis patients received by intravenous injection between 1.2 and 2.4 milligrams of I¹³¹-labeled gamma globulin with a radioactivity of between 29.1 to 152 microcuries. Blood samples were obtained. The amount of I¹³¹ activity was determined in the serum, in urine, and by whole-body techniques. Cerebrospinal fluid samples were obtained by spinal taps. The procedure was repeated with selected subjects, using 29 to 152 microcuries of gamma globulin labeled with I¹³¹ injected intravenously.

This study showed that gamma globulin transferred about 12 times faster from the cerebrospinal fluid to the plasma than the reverse path. This research was supported in part by the National Multiple Sclerosis Society and the U.S. Atomic Energy Commission.

References

Lippincott, S.W., S. Korman, L.C. Lax, and C. Corcoran. ATransfer Rates of Gamma Globulin Between Cerebrospinal Fluid and Blood Plasma (Results Obtained on a Series of Multiple Sclerosis Patients).@Journal of Nuclear Medicine. Vol. 6, 1966, pp. 632B644.  "

BNL-45. Study of the Metabolism of Scandium Using Scandium-46 as Tracer

IN 1964, researchers at the Veterans Administration Hospital, Hines, Illinois, and Brookhaven National Laboratory conducted a collaborative study of the metabolism, tissue distribution, and biological turnover of radioactive scandium using scandium-46 (Sc⁴⁶) as a tracer. Study subjects were six male and six female patients, ranging in age from 52 to 77 years, with various chronic diseases, including cancer.

Fifty microcuries of several Sc⁴⁶-labeled compounds were administered intravenously. Blood samples were drawn 1, 4, 8, 24, 48, and 72 hours after administration of the tracer. Urine and stool samples were collected throughout the study. Scandium retention in the body was measured by whole-body counting of selected subjects over a period of 1 to 7 months. Tissue samples were obtained at autopsy from three subjects who died as a consequence of their disease during the study, and levels of Sc⁴⁶ were measured.

This experiment showed that scandium uptake was greatest in the spleen and that the biological retention half-time was about 1,400 days. This research was supported by the U.S. Atomic Energy Commission.

References

Rosoff, B., and H. Spencer. AMetabolism of Scandium-46 in Man.@International Journal of Applied Radiation and Isotopes.Vol. 16, 1965, pp. 479B485.  "

BNL-46. Use of Whole-Body Counting to Evaluate the Metabolism of Proteins Labeled with Iodine-131

IN APPROXIMATELY 1964, researchers from the Medical Research Center of Brookhaven National Laboratory, in collaboration with medical personnel from the Jewish Chronic Disease Hospital, New York and the Bowman Gray School of Medicine at Wake Forest University, North Carolina conducted an extensive study on serum proteins in neoplastic (abnormal cell growth, such as a tumor) diseases.

Two proteins, gamma globulin and albumin, both labeled with iodine-131 (I¹³¹), were administered to normal subjects and patients with various diseases (including multiple myeloma, breast cancer, and lymphoma) to measure the degradation rate of these proteins in the serum. Iodine-131Blabeled gamma globulin and albumin containing 17 to 60 microcuries of I¹³¹ were administered by injection. Serum and urine samples were measured for radioactivity and total-body counting techniques were conducted to measure retention and clearance times. Over 70 subjects were employed in this study and monitoring continued for as long as 60 days.

In addition to establishing the turnover rate of proteins in certain diseases, this experiment demonstrated that whole-body counting was preferred over serum/urine sampling for accuracy and simplicity. This research was supported by the U.S. Atomic Energy Commission.

References

Cohen, S.H., S.W. Lippincott, and S. Korman. AProtein Metabolism in Neoplastic Diseases Using the Whole-Body Counting Technique.@In Clinical Uses of Whole-Body Counting: Proceedings of a Panel, International Atomic Energy Agency. Vienna, Austria, June 28BJuly 2, 1965, pp. 212B231.  "

BNL-47. Study of Skeletal Discrimination Between Calcium and Strontium Using Calcium-47 and Strontium­85

A STUDY WAS CONDUCTED at Brookhaven National Laboratory during 1964 to 1965 on the uptake and metabolism of calcium and strontium in bone. Calcium and strontium are chemically similar, and the purpose of this study was to determine whether the skeleton discriminates between uptake of strontium and calcium during normal bone formation. Seven healthy male subjects ranging in age from 53 to 80 years were selected for this study and placed on a regulated diet in the metabolic ward of the hospital.

Plasma calcium levels were evaluated and found to be within normal range before the subjects were injected intravenously with 20 microcuries of calcium-47 (Ca⁴⁷) and 15 microcuries of strontium-85 (Sr⁸⁵) as chlorides. Concentrations of Ca⁴⁷ and Sr⁸⁵ were measured in 24-hour urine and fecal specimens daily for 10 days. Plasma concentrations of Ca⁴⁷ and Sr⁸⁵ were also measured periodically for 10 days. The whole-body retention of Ca⁴⁷ and Sr⁸⁵ was determined by direct in vivo counting in the Brook-haven whole-body counter for 30 days post-injection.

This study showed that strontium predicted calcium uptake, retention, and excretion, but that calcium was slightly preferred to strontium by the skeleton as a mineral constituent. This research was supported by the U.S. Atomic Energy Commission.

References

Cohn, S.H., S.R. Bozzo, J.E. Jesseph, C. Constantinides, E.A. Gusmano, and J.S. Robertson. AStrontium and Calcium Skeletal Discrimination Determined by Compartmental Analysis.@Journal of Applied Physiology. Vol. 21, 1966, pp. 67B72.  "

BNL-48. Evaluation of Thyroid Function and Anatomy Using Technetium-99m Pertechnetate and Iodine-131

BETWEEN 1964 AND 1966, a study was conducted at Brookhaven National Laboratory to evaluate thyroidal uptake of technetium-99m pertechnetate (Tc^99mO₄) relative to health status of the subject, and to compare this imaging procedure with other thyroid function tests. A total of 208 studies were conducted using 193 patients hospitalized for evaluation of suspected thyroid disease or for other non-thyroidBrelated reasons.

Between 2.0 and 2.6 millicuries ofTc^99mO₄ were administered intravenously to the subjects, and its distribution was monitored in the 143 non-thyroidBsuppressed subjects, using a sodium iodide (NaI) crystal detector over the neck area. A phantom containing 3 percent of the activity administered to the subjects was used as the standard. Many patients also underwent a protein-bound iodine test before or after the Tc^99mO₄ study; the test used an unreported amount of iodine-131 (I¹³¹) given orally, followed by thyroid counting for 1¹³¹ for 24 hours. Blood samples obtained from 47 patients after the Tc^99mO₄ scanning procedure were analyzed to determine the Tc^99m activity per liter of plasma. Thyroid size, the ratios of Tc^99mO₄ in the thyroid to that in the plasma, and thyroid technetium space were calculated.

Technetium-99m pertechnetate imaging was found to have some advantages over the I¹³¹ test in the diagnosis and monitoring of thyroid disease, and was recommended for physiological and anatomical studies of the thyroid. This study was supported by the U.S. Atomic Energy Commission.

References

Atkins, H.L., and P. Richards. AAssessment of Thyroid Function and Anatomy with Technetium-99m as Pertechnetate.@Journal of Nuclear Medicine. Vol. 9, No. 1, January 1968, pp. 7B15.  "

BNL-49. Metabolic Study of Technetium-99m-DTPA as an Improved Brain and Kidney Scanning Agent

IN THE LATE 1960s, researchers at the Medical Research Center of Brookhaven National Laboratory studied the metabolism of diethylenetriaminepentaacetic acid labeled with technetium-99m (Tc^99m-DTPA) as a basis for its use as an improved brain and kidney scanning agent. Hospitalized patients participated in the study.

Five hundred microcuries of Tc^99m-DTPA were administered intravenously to each of 12 subjects believed to be free of kidney disease. Retention of activity was evaluated in a whole-body counter. Blood and 24-hour urine samples were measured to determine the Tc^99m-DTPA excreted by the body. Two patients received injections of 3 microcuries of Tc^99m-DTPA and were whole-body counted several times over a 24-hour period. Three patients were injected with 12 millicuries of Tc^99m-DTPA and underwent several profile scans during the following two hours. A single patient received 13 millicuries and was whole-body scanned after 1 hour. One patient was injected with 14 millicuries and underwent seven serial kidney scans during the following 2 hours. It is unclear whether the latter 7 patients were a subset of the first 12, or if the original subject pool was actually 19.

The results indicted that Tc^99m-DTPA is distributed uniformly throughout the extracellular space without concentration in any organ and is rapidly cleared from the body.

The study further showed that Tc^99m-DTPA is effective as a brain and kidney imaging agent and also has use as an imaging agent in vascular studies. This study was funded by the U.S. Atomic Energy Commission.

References

Hauser, W., H.L. Atkins, K.G. Nelson, and P. Richards. ATechnetium-99m DTPA: A New Radiopharmaceutical for Brain and Kidney Scanning.@Radiology. Vol. 94, No. 3, March 1970, pp. 679B684.  "

BNL-50. Study of Tryptophan Metabolism in Humans with Various Types of Anemia Using Carbon-14

IN THE LATE 1960s, Brookhaven National Laboratory researchers studied tryptophan metabolism in humans with various types of anemia using tryptophan labeled with carbon-14 (C¹⁴ ) as a tracer. The purpose of this study was to identify abnormalities in tryptophan metabolism in advanced anemia. Seven hospitalized patients, ranging in age from 12 to 67 years, with red cell anemias were selected as study subjects.

Tryptophan (approximately 12 to 31 milligrams) with approximately 100 microcuries of C¹⁴ was administered orally to each patient with a loading dose (2 grams) of unlabeled tryptophan. Exhaled carbon dioxide was collected from each subject for 27 hours to be analyzed for C¹⁴O₂. Urine was also collected and analyzed for C¹⁴ levels.

Study results indicated abnormal enzyme activities. Some enzymes involved in tryptophan metabolism are associated with some types of anemias. The study was supported by the U.S. Atomic Energy Commission.

References

Hankes, L., R. Brown, L. Schiffer, and M. Schmaeler. ATryptophan Metabolism in Humans with Various Types of Anemias.@Blood: The Journal of Hematology. Vol. 32, No. 4, October 1968, pp. 649B661.  "

BNL-51. Studies on the Effects of a High-Calcium Diet on Osteoporosis, Using Calcium-47

IN 1967,SCIENTISTS at the Medical Research Center of Brookhaven National Laboratory conducted a study of the role of dietary calcium in osteoporosis in humans. Seven patients, including two females and five males ranging in age from 58 to 89 years, participated in the study. All exhibited slight to severe symptoms of osteoporosis. Five of the seven were non-ambulatory as a result of the disease.

Subjects were fed a diet high in calcium and phosphorus for approximately 20 days. During the latter 10 days, calcium-47 (Ca⁴⁷) tracer studies were conducted. Each patient received 25 microcuries of Ca⁴⁷ as calcium chloride by intravenous injection. Blood samples were drawn at 1 and 6 hours and daily thereafter for 10 days postinjection. Complete 24-hour collection of urine and feces and whole-body counting was continued for 10 days to measure retention of Ca⁴⁷ by the body. Patients then received a calcium supplement for an additional 20 days. During the latter 10 days of this period, the tracer study was repeated.

This study showed that a diet high in calcium had a small, positive impact on osteoporosis. This work was funded by the U.S. Atomic Energy Commission.

References

Cohn, S.H., C.S. Dombrowski, W. Hausner, and H.L. Atkins. AHigh Calcium Diet and the Parameters of Calcium Metabolism in Osteoporosis.@The American Journal of Clinical Nutrition. Vol. 21, No. 11, 1968, pp. 1,246B1,253.  "

BNL-52. Studies on the Conversion of Pyruvate and Lactate to Glucose Using Carbon-14

A COLLABORATIVE STUDY was conducted in 1968 by researchers at Brookhaven National Laboratory and Case Western Reserve University, Cleveland, Ohio, on the conversion of lactate and pyruvate to glucose. Three normal subjectsCtwo males and one female between 22 and 42 years of ageCwere studied at the Clinical Research Center, University Hospital, Cleveland.

After fasting overnight, the subjects were injected with 50 microcuries of sodium L­lactate-3 labeled with carbon-14 (C¹⁴). The remaining six subjects, all females between the ages of 17 and 64, were studied at the Medical Research Center, Brookhaven National Laboratory. Three of these subjects were administered 50 microcuries of C¹⁴-labeled DL-lactate-2; the others received 50 microcuries of C¹⁴-labeled pyruvate-2. A blood sample was obtained from each subject 1 hour after injection and the glucose isolated and measured for radioactivity.

The results of this study suggested that metabolism of lactate in humans followed the observed path for animals. The study was funded by the National Institutes of Health and the U.S. Atomic Energy Commission.

References

Hostetler, K.Y., H.R. Williams, W.W. Shreeve, and B.R. Landau. AConversion of Specifically Carbon-14BLabeled Lactate and Pyruvate to Glucose in Man.@The Journal of Biological Chemistry. Vol. 244, No. 8, April 1969, pp. 2,075B2,077.

Memorandum. W.W. Shreeve and A.R. Hennes to the BNL Committee for the Use of Isotopes in Humans. March 25, 1957. Brookhaven National Laboratory Project H-48, Brookhaven National Laboratory. Clinical Research Center, Bldg. 490, Human Medical Research Protocols.  "

BNL-53. Study of Glucose Metabolism in Patients with Gout Using Carbon-14 B Labeled Glucose

IN 1968, RESEARCH findings were published describing the metabolic pathway of sugar (glucose) in patients with elevated levels of uric acid (hyperuricemia) and gout. This study was conducted at the Intermediary Metabolism Research Unit, University of Natal, Durban, South Africa. A researcher from Brookhaven National Laboratory also collaborated on the study. A group of 10 male patients, ages 39 to 51 years, with elevated blood uric acid levels was studied. Eight of these 10 had experienced previous attacks of gout. Ten males subjects, ages 37 to 47 years, with normal uric acid levels were included as controls. Five of the 10 hyperuricemic patients had histories of abnormal glucose tolerance, as did 3 of the control group. All subjects in the study were Indian.

All subjects fasted for approximately 10 hours before testing and were given an oral glucose load to which had been added glucose labeled with carbon­14 (C¹⁴). The test was repeated 2 days later, using glucose-6BC¹⁴. Approximately 25 microcuries of C¹⁴ were used in each test, except for two cases where individuals received 50 microcuries of each labeled compound. Respired carbon dioxide was collected from subjects 60 and 120 minutes after administrations of the radioactive material for C¹⁴O₂ analysis. Blood samples were drawn at the same time. Radioactivity levels were measured in the samples.

The study showed that glucose was metabolized in essentially the same way by both groups. This work was supported in part by the South African Energy Board, the South Africa Council for Science and Industrial Research, the Rockefeller Foundation, and the U.S. Atomic Energy Commission.

References

Kallie, R.N., W.W. Shreeve, S.M. Joubert, and M.C. Path. AStudies in Primary Hyperuricemia III. The Conversion of C¹⁴ to Breath C¹⁴O₂ From Glucose-1-C¹⁴ and Glucose-6-C¹⁴ in Hyperuricemia and Gout.@South African Medical Journal. May 1, 1968. pp. 473B476.  "

BNL-54. Experimental Lymph Node Imaging with Technetium-99m Sulfur Colloid

IN 1968 TO 1970, scientists at the Medical Research Center of Brookhaven National Laboratory conducted experiments to determine the suitability of technetium-99m (Tc^99m)Bsulfur colloid for imaging lymph nodes. Subjects for this study included an unstated number of cancer patients with various malignancies. The lymph node studies were not considered an essential aspect of patient management.

A gelatin-stabilized preparation of Tc^99m-sulfur colloid was prepared. After testing the preparation in laboratory animals, the Tc^99m-sulfur colloid was administered in amounts of 240 to 1,800 microcuries by subcutaneous injection to the feet of the cancer patients. In addition, a female patient with metastatic breast cancer was administered 2,200 microcuries of Tc^99m-sulfur colloid subcutaneously in the left side of her abdomen. The uptake and retention of the injected material in nearby lymph nodes was measured by rectilinear scanning and a scintigraph camera.

The results of this study showed that the best time to scan was 2.5 to 3 hours after injection. The investigators concluded that this technique had application for diagnostic imaging of Hodgkin=s disease (a malignancy of the lymphatic system). These studies were supported by the U.S. Atomic Energy Commission.

References

Atkins, H., W. Hauser, and P. Richards. AVisualization of Mediastinal Lymph Nodes after Intraperitoneal Administration of Tc^99m-Sulfur Colloid.@Nuclear Medicine. Vol. 9, No. 3, October 1970, pp. 275B278.

Hauser, W., H.L. Atkins, and P. Richards. ALymph Node Scanning with Tc^99m-Sulfur Colloid.@Radiology. Vol. 92, No. 6, May 1969, pp. 1,369B1,371.  "

BNL-55. The Comparison of Two Forms of Tryptophan in Patients with Scleroderma, Using Carbon-14 as a Tracer

FROM 1968 TO 1971, researchers from Brookhaven National Laboratory conducted a study to compare the metabolic patterns of two forms of tryptophan (the D- and L-isomers) in patients with scleroderma (chronic hardening and shrinking of connective tissue in any organ of the body, including the skin) using tryptophan compounds labeled with carbon-14 (C¹⁴) as a tracer. The purpose of this study was to evaluate abnormal tryptophan metabolism in scleroderma patients. The study subjects were five females with scleroderma, ranging in age from 40 to 60 years.

Each subject was given orally between 17 and 113 milligrams of one or more forms of C¹⁴ -labeled tryptophan, having between 10 and 114 microcuries C¹⁴, together with 2 grams of unlabeled L-tryptophan. Fifteen-minute samples of expired C¹⁴O₂ were collected for a 4-hour period after the administration and at 2-hour intervals thereafter, and were analyzed for C¹⁴ activity. Four consecutive 24-hour urine collections were also analyzed.

The study showed that scleroderma patients have an altered metabolic step in the tryptophan metabolic pathway. This study was supported in part by the American Cancer Society, the National Cancer Institute, and the U.S. Atomic Energy Commission.

References

Hankes, L., R. Brown, J. Lekelm, M. Schmaeler, and J. Jesseph. AMetabolism of C¹⁴-Labeled Enantiomers of Tryptophan, Kynurenine, and Hydroxynurenine in Humans with Scleroderma.@The Journal of Investigative Dermatology. Vol. 58, No. 2, 1972, pp. 85B95.  "

BNL-56. Metabolic Studies on Normal and Acromegalic Subjects Using Carbon-14 B Labeled Pyruvate

IN 1969, RESEARCHERS from Brookhaven National Laboratory and the Department of Endocrinology and Metabolism at Karolinska Hospital, Stockholm, Sweden, collaborated on a study of human metabolism of pyruvate. A total of 32 studies were performed on 6 acromegalic patients and 17 non-acromegalic subjects. (Acromegaly is an endocrine disorder also called pituitary gigantism that is characterized by abnormal growth and swelling of the face, hands, and feet.)

Four of the non-acromegalic (normal) subjects were given human growth hormone prior to the study. All subjects were administered 20 microcuries of carbon-14Blabeled pyruvate (2-C¹⁴-sodium-pyruvate) by intravenous injection. This was followed by injection of 100 microcuries of tritium (H³)-labeled water in normal saline. Patients remained at bed rest for 2 hours. Breath samples were collected at 15, 30, 60, and 120 minutes after injection and analyzed for C¹⁴-labeled carbon dioxide. One hour after injection, a blood sample was drawn and analyzed for labeled and unlabeled glucose, free fatty acids, and H³-labeled water.

These studies showed that acromegalics with a diabetic tendency exhibited a lowered glucose tolerance and impaired pyruvate oxidation. This study was supported by the U.S. Public Health Service and the U.S. Atomic Energy Commission.

References

Shreeve, W.W., E. Cerasi, and R. Luft. AMetabolism of [2-C¹⁴]-Pyruvate in Normal, Acromegalic, and HGH-Treated Human Subjects.@Acta Endocrinologica. Vol. 65, 1970, pp. 155B169.  "

BNL-57. Measurement of Whole-Body Potassium Using Potassium-42 as Tracer and a Cesium-137 Gamma Source

scientists in the Medical Department of Brookhaven National Laboratory, examined the total-body distribution of potassium using potassium-42 (K⁴²) as a tracer and a whole-body counter. Objectives included in vivo calibration of the counter and determination of the normal range of potassium values as a function of age, gender, body weight, and other parameters. Participating in the study as subjects were 425 normal volunteers, including obese children.

Some subjects were administered K⁴²; oIN 1969 AND 1970, thers were exposed to a broad beam cesium-137 (Cs¹³⁷) source. Total body counts were taken at 0.5, 3, 6, 24, and 30 hours after intravenous injection of 0.3 microcurie of K⁴². Subjects also were counted over a broad beam Cs¹³⁷ source to determine the absorption correction factor for potassium-40 (K⁴⁰) in the body. As part of a study on the measurement of lean body mass, the grossly obese children and the children of normal body weight were orally administered 0.1 microcurie of K⁴² and were then counted in the whole-body counter to compare measurement results. The levels of potassium in the study population were measured and expressed as a function of age and gender.

The study showed that the calibration factor was about "3 percent for the study group, which varied in body weight from 26.8 to 145.5 kilograms. This work was supported by the U.S. Atomic Energy Commission.

References

Cohn, S.H., and C.S. Dombrowski. AAbsolute Measurement of Whole-Body Potassium by Gamma Ray Spectrometry.@Journal of Nuclear Medicine. Vol. 11, No. 6, June 1970, pp. 239B246.  "

BNL-58. Studies on the Kinetics of Halothane Using Bromine-82

IN THE EARLY 1970s, researchers at the Medical Department of Brookhaven National Laboratory; the Department of Anesthesiology of Columbia University, New York; and the University of Liverpool, England, conducted collaborative studies on the uptake, distribution, and excretion of halothane, an inhalation anesthetic, that had been labeled with radioactive bromine-82 (Br⁸²).

Four volunteer subjects inhaled 2.5 microcuries of Br⁸²-labeled halothane in a single breath. Activity in the body was measured by whole-body counting at 1-minute intervals. Subjects also received an oral administration of 2.5 microcuries of Br⁸²-labeled ammonium bromide to determine, by comparison, whether Br⁸² dissociated from the halothane after administration.

The study showed that concentrations of halothane were initially high in upper parts of the body and low in lower parts of the body. Diffusion equilibrium throughout the body was reached in about 24 minutes. This work was supported by the U.S. Atomic Energy Commission.

References

Mark, L.C., I.C. Geddes, J.R. Scherrer, C.S. Dombrowski, and S.H. Cohn. APharmacokinetics of Halothane in Man: A Novel Approach.@International Journal of Applied Radiation and Isotopes. Vol. 22, 1971, pp. 171B175.  "

BNL-59. Comparison of Technetium-99m and Iodine-123 for Thyroid Imaging

IN THE EARLY 1970s, researchers in the Medical and Chemistry Departments of Brookhaven National Laboratory, evaluated technetium-99m (Tc^99m) and iodine-123 (I¹²³) to determine their relative effectiveness as thyroid imaging agents. One hundred patients were included in the study. Of these, 5 were hypothyroid (having abnormally low thyroid activity), 77 were euthyroid (having normal thyroid activity), 15 were hyperthyroid (having abnormally high thyroid activity), 2 had chronic thyroiditis, and 1 had subacute thyroiditis.

Each subject first received between 2.5 and 3.0 millicuries of Tc^99m pertechnetate (Tc^99mO₄) intravenously and was examined by a gamma camera scanning instrument 30 minutes later. Iodine-123 (100 to 350 microcuries) as sodium iodide was then administered orally to most subjects; some received 60 to 75 microcuries of I¹²³. Uptake measurements and scintiphoto-graphic images were obtained 18 hours later. Two patients participated in repeat studies.

Overall, I¹²³ was found to be superior to Tc^99m as a thyroid imaging agent. This was attributed to the greater concentration of I¹²³ in the thyroid, although some unexplained discrepancies between Tc^99m and I¹²³ images were found. This research was funded by the U.S. Atomic Energy Commission.

References

Atkins, H.L., J.F. Klopper, R.M. Lambrecht, and A.P. Wolf. AA Comparison of Technetium-99m and Iodine-123 for Thyroid Imaging.@The American Journal of Roentgenology, Radium Therapy and Nuclear Medicine. Vol. 117, No. 1, January 1973, pp. 195B201.  "

BNL-60. Studies on Calcium Metabolism and Chronic Renal Failure Using Calcium-47

IN A COLLABORATIVE STUDY conducted in the early 1970s, researchers at the Medical Research Center of Brookhaven National Laboratory, the Nassau County Medical Center, and the Health Sciences Center, State University of New York at Stony Brook, investigated calcium metabolism in humans with chronic renal (kidney) failure using calcium-47 (Ca⁴⁷) as a tracer. Study subjects were two groups of patients with chronic renal failure who had undergone treatment for kidney disease prior to the study. The first group consisted of four males and two females between 46 and 63 years of age with slight-to-mild kidney failure. The second group consisted of seven subjectsCfive females and two males between the ages of 17 and 53 yearsCwith severe kidney failure.

All subjects ingested a constant diet with fixed calcium and phosphorus levels for 7 days before and 10 days after administration of the Ca⁴⁷ tracer. Experimental subjects received 20 microcuries of Ca⁴⁷ intravenously. The level of Ca⁴⁷ was measured in the blood 1 and 6 hours after injection and daily thereafter for the next 9 days. Stool and urine samples were collected over a 24-hour period and monitored for radioactivity. The concentration of Ca⁴⁷ remaining in the body was measured with the Brookhaven whole-body counter.

This experiment showed that calcium metabolism in the group with mild kidney failure did not differ significantly from the normal population. Those with severe kidney failure exhibited a number of significant changes in the metabolism of calcium and phosphorus. This research was funded in part by the U.S. Atomic Energy Commission.

References

Letteri, J. M., K.J. Ellis, D.P. Orofino, S. Ruggieri, S.N. Asad, and S.H. Cohn. AAltered Calcium Metabolism in Chronic Renal Failure.@Kidney International. Vol. 6, 1974, pp. 45B54.  "

BNL-61. Studies of Glucose Tolerance in Obese Humans Using Glucose Labeled with Carbon-14 and Tritium

IN APPROXIMATELY 1970, researchers at Brookhaven National Laboratory used glucose (simple sugar) labeled with carbon-14 (C¹⁴) and tritium (H³) to study the human response to cortisone glucose tolerance testing. Ten female subjects of normal weight between 17 and 35 years of age, and 19 obese females between 17 and 52 years of age, were included in the study. All nonobese subjects were in the hospital for at least 48 hours prior to metabolic studies and on diets of 1,600 to 2,000 calories, with 200 to 250 grams of carbohydrates per day. Obese subjects received 1,800 to 2,000 calories daily, with 200 to 300 grams of carbohydrates.

All subjects received an oral dose of glucose in an amount proportional to body-surface area. The glucose contained 40 to 50 microcuries of glucose-1-C¹⁴ and 250 to 500 microcuries of glucose-1-H³. Blood samples were drawn at 30-minute intervals and analyzed for tritiated glucose and tritiated water. Breath was monitored almost continuously for C¹⁴O₂. Body water space was also determined using tritiated water (250 to 500 microcuries of H³OH) administered intravenously to the fasting subjects. Blood samples were drawn at 1 and 2 hours to measure H³ activity. All subjects also received a conventional, unlabeled intravenous cortisone glucose tolerance test.

This study indicated metabolic differences between obese and nonobese subjects. This research was supported by the U.S. Atomic Energy Commission.

References

Shreeve, W.W., A.J. Tashjian, N. Oji, R.H. Slavinski, and M. Hoshi. AFormation of C¹⁴O₂ and H³OH from Glucose-1-C¹⁴, -1-H³ During Oral Cortisone Glucose Tolerance Tests in Obese Patients.@Metabolism. Vol. 20, No. 3, March 1971, pp. 280B292.  "

BNL-62. Measurement of Total-Body Calcium, Sodium, Chlorine, Nitrogen, and Phosphorus by Neutron Activation Analysis

IN 1970 AND 1971, researchers at the Medical Research Center of Brookhaven National Laboratory examined the feasibility of using neutron activation analysis to measure levels of total-body calcium, sodium, chlorine, phosphorus, and nitrogen in humans. A total of 17 patients ranging in age from 15 to 70 years participated as subjects. This group consisted of four females with metastatic breast cancer, four females and two males with osteoporosis, two females with chronic kidney failure, and one male with Cushing=s disease.

The subjects were exposed to a uniform neutron depth flux from 14-MeV (million electron volt) neutrons. Two 15-minute counts were then taken, using a whole-body counter.

The results indicated that the amounts of calcium, sodium, chlorine, nitrogen, and phosphorus in the subjects=bodies could be determined using neutron activation. The average radiation dose to patients using this technique was estimated to be 0.637 rem. The researchers concluded that the technique held promise for use in medical research and diagnosis. This work was supported by the U.S. Atomic Energy Commission.

References

Cohn, S.H., C.S. Dombrowski, and P.G. Fairchild. AIn Vivo Neutron Activation Analysis of Calcium in Man.@International Journal of Applied Radiation and Isotopes. Vol. 21, 1970, pp. 127B137.

Cohn, S.H., and C.S. Dombrowski. AMeasurement of Total-Body Calcium, Sodium, Chlorine, Nitrogen, and Phosphorus in Man by In Vivo Neutron Activation Analysis.@Journal of Nuclear Medicine. Vol. 12, No. 7, July 1971, pp. 499B505.  "

BNL-63. Effectiveness of Technetium-99m-DTPA in Measuring Glomerular Filtration Rate

IN 1970 AND 1971, researchers at Brookhaven National Laboratory compared the effectiveness of technetium-99m-diethylenetriamine-pentaacetic acid (Tc^99m-DTPA) with that of sodium iothalamate labeled with iodine-125 (I¹²⁵), for measuring glomerular filtration rates in evaluation of kidney disease. Technetium-99m and I¹²⁵ were used as tracers in this study. The subjects were 11 patients under investigation for hypertension (high blood pressure) who had normal or slightly diminished kidney function, as determined by other methods.

Each subject received a single intravenous injection of approximately 3 millicuries of Tc^99m-DTPA and 50 microcuries of I¹²⁵-sodium iothalamate. Urine samples and nine blood samples were obtained from each patient at regular intervals during the 24 hours after the administration. Measures of plasma concentration and urinary excretion of Tc^99m-DTPA were obtained from each subject, using a known standard of Tc^99m-DTPA for comparison.

The results indicated that Tc^99m-DTPA, rapidly prepared by a kit method, was an effective agent for measuring glomerular filtration rates in suspected kidney disease. This research was supported by the U.S. Atomic Energy Commission.

References

Klopper, J.F., W. Hauser, H.L. Atkins, W.C. Eckelman, and P. Richards. AEvaluation of Tc^99m-DTPA for the Measurement of Glomerular Filtration Rate.@Journal of Nuclear Medicine. Vol. 13, No. 1, January 1972, pp. 107B110.  "

BNL-64. Total-Body Neutron Activation Analysis

BETWEEN 1970 AND 1972, scientists at the Medical Research Center of Brookhaven National Laboratory, developed a method for analyzing total-body content of the elements calcium, sodium, chlorine, aluminum, and potassium. This method involved exposing a subject to a broad-beam neutron source and counting certain neutron-activation products in the human, using a whole-body counter. The neutrons were generated by an external plutonium-238, beryllium oxide (Pu²³⁸O₂-Be) neutron source as fourteen 50-curie sources arranged in a planar array. The levels of nitrogen-13, calcium-49, sodium-24, chlorine-38, and aluminum-28 produced in the body by neutron activation were determined from the resulting gamma-ray spectrum.

One male subject was irradiated for 5 minutes, then counted 3 minutes after exposure. The same patient was later exposed to a source of 14-MeV (million-electron-volt) neutrons (from an accelerator) and counted 6 minutes after exposure for comparison of activation product spectra. The radiation absorbed dose to the subject was estimated to be 277 millirems for each exposure.

The results of the study indicated that the plutonium/beryllium array produced a neutron source that was more uniform than the 14-MeV neutron source for total-body neutron activation analysis and body composition studies. This research was supported by the U.S. Atomic Energy Commission.

References

Cohn, S.H., K.K. Shulka, C.S. Dombrowski, and R.G. Fairchild. ADesign and Calibration of a >Broad-Beam=Pu²³⁸O₂-Be Neutron Source for Total-Body Neutron Activation Analysis.@Journal of Nuclear Medicine. Vol. 13, No. 7, July 1972, pp. 487B492.  "

BNL-65. Study of the Effects of a High-Sucrose Dietary Intake Using Carbon-14

IN 1973, researchers at Brookhaven National Laboratory studied the acute and chronic effects of a high-sucrose (table sugar) diet intake on plasma triglyceride (a form of fatty acid) levels in comparison to those produced by a high-starch diet. Twenty females and three males between the ages of 16 and 47 years were included in the study. All but two females and one male were grossly overweight.

Subjects were hospitalized and given a diet consisting of 2,200 to 3,000 calories per day, of which 50 percent were from carbohydrate, 15 percent from protein, and 35 percent from fat. After overnight fasting, subjects received an oral dosage of sucrose labeled with 40 microcuries of carbon-14 (C¹⁴). Blood was sampled frequently during the first 3 hours for measurement of C¹⁴-labeled glucose and at 0, 1, 3, 6, and 12 hours for C¹⁴-labeled triglycerides in the plasma. Breath was collected during the first 3 hours after ingestion and measured for C¹⁴-labeled carbon dioxide. Other diets were also studied.

Among other findings, this experiment showed that triglycerides peaked very rapidly (3 to 6 hours) after ingestion of sugar. This research was funded by the U.S. Atomic Energy Commission.

References

Wu, C.H., M. Hoshi, and W.W. Shreeve. AHuman Plasma Triglyceride Labeling after High-Sucrose Feeding. I. Incorporation of Sucrose-U-C¹⁴.@Metabolism. Vol. 23, No. 12, December 1974, pp. 1,125B1,139.  "

BNL-66. Studies of the Uptake of Metabolites of Tryptophan Using Carbon-14

IN THE MID 1970s, researchers at Brookhaven National Laboratory studied the uptake of metabolites of tryptophan using carbon-14 (C¹⁴) as a tracer. This was done to determine if reliable metabolism studies could be conducted using tryptophan and several of the isomers labeled with C¹⁴, and if tryptophan metabolites are bound to proteins in blood. Study subjects were volunteers and included five white female scleroderma patients 40 to 60 years in age.

Tryptophan, or D- or L-kynurenine, or D- or 1-3-hydroxykynurenine was administered to each subject in amounts ranging from 10 to 50 microcuries of C¹⁴, depending on the compound. Ten milliliters of blood were drawn from each subject after administration of tryptophan and analyzed for C¹⁴ content.

The study provided new information on metabolites and showed that the amino acids were bound to proteins in circulating blood. This study was supported in part by the U.S. Department of Health, Education, and Welfare and the U.S. Energy Research and Development Administration.

References

Hankes, L., and M. Schmaeler. AThe Uptake of C¹⁴-Labeled Hydroxanthranilic Acid and Enantiomers of Tryptophan, Kynurenine, and Hydroxykynurenine in Human Blood.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 149, 1975, pp. 1,063B1,068.  "

BNL-67. Comparison of Tryptophan Metabolism Using Carbon-14BLabeled Tryptophan

IN 1975 AND 1976, Brookhaven National Laboratory researchers collaborated with the South African Atomic Energy Board, Pretoria, South Africa, to evaluate tryptophan metabolism in South African gold miners and compare it with that of previously studied American female scleroderma patients. Six white male patients at a South African hospital volunteered for the study. These subjects were between 40 and 60 years of age and suffering from silicosis-induced scleroderma.

A 2-gram loading dose of unlabeled tryptophan was administered to each subject. Five days later, 9 to 31 milligrams of carbon-14 (C¹⁴)Blabeled tryptophan kynurenine-keto, or hydroxy-l-kynurenine-keto labeled with 21 to 26 microcuries of C¹⁴ was orally administered to each subject 1 hour after breakfast. Urine was collected for consecutive 24-hour periods after administration and analyzed for C¹⁴ activity.

This study confirmed the earlier finding that some scleroderma patients have an altered step in the tryptophan metabolic pathway. The relationship between silicosis of the lung and later development of scleroderma was unexplained by the study. The study was supported by the South African Council for Scientific and Industrial Research, the National Institutes of Health, and the U.S. Energy Research and Development Administration.

References

Hankes, L., E. DeBruin, C. Jansen, L. Vorster, and M. Schmaeler. AMetabolism of C¹⁴-Labeled L-tryptophan, L-kynurenine, and Hydroxy-L-Kynurenine in Miners with Scleroderma.@SA Medical Journal. Vol. 51, March 19, 1977, pp. 383B390.  "

BNL-68. Changes in Body Composition with Age Determined by Total-Body Neutron Activation Analysis

IN 1975 AND 1976, several related studies were conducted at Brookhaven National Laboratory involving use of total-body neutron activation analysis to determine body levels of calcium, phosphorus, and potassium. The populations studied included 40 white women, 39 white men, 28 black women, and 21 black men. Each of the subjects received a 5-minute total-body exposure to a planar array of 14 neutron radiation sources. The source of external neutrons was 14 capsules each containing 50 curies plutonium-238 mixed with beryllium. The neutron flux activated stable elements in the irradiated subject, and the subsequent gamma emissions from the body were then counted in the Brookhaven whole-body counter.

In the first study, the age-related changes in body chemical composition were measured in a normal black population ranging in age from 30 to 80 years. The levels of total-body calcium, phosphorus, sodium, and chlorine were measured by gamma counting for neutron-induced calcium-49, aluminum-28, sodium-24, and chlorine-38. These data were compared to values observed on a normal white population in a previous study. This study showed that black men and women had significantly higher total-body calcium, phosphorus, sodium, chlorine, and potassium than that of a white population with the same ages and sex. However, the rates of mineral loss with aging were similar.

Two additional studies reported changes in body chemical composition with age in adult males and females and the effect of aging on bone mass mineral loss in adult women. These studies showed that women lose calcium at 0.37 percent per year before the age of 50 and 1.1 percent per year afterwards, and that men lose calcium at 0.7 percent per year. The rates of total-body phosphorus and potassium loss are directly related to that of calcium. These studies were supported by the U.S. Energy Research and Development Administration.

References

Cohn, S.H., C. Abesamis, I. Zanzi, J.F. Aloia, S. Yasumura, and K.J. Ellis. ABody-Elemental Composition: Comparison Between Black and White Adults.@American Journal of Physiology. Vol. 232, No. 4, pp. E419BE422.

Cohn, S.H., A. Vaswani, I. Zanzi, and K.J. Ellis. AEffect of Aging on Bone Mass in Adult Women.@American Journal of Physiology. Vol. 230, No. 1, January 1976, pp. 143B148.

Cohn, S.H., A. Vaswani, I. Zanzi, J.F. Aloia, M.S. Roginsky, and K.J. Ellis. AChanges in Body Chemical Composition with Age Measured by Total-Body Neutron Activation.@Metabolism. Vol. 25, No. 1, Jan. 1976, pp. 85B96.  "

BNL-69. Study of Krypton-79 Biokinetics

IN 1976, investigators of the Applied Science and Medical Departments, Brookhaven National Laboratory, studied the total-body retention and clearance of krypton gas using the isotope krypton-79 (Kr⁷⁹). Krypton is a noble gas produced during uranium fission in nuclear power plants (mainly Kr⁸⁵), and little information was available at that time on the metabolism of krypton in man. The purpose of this study, therefore, was to determine the uptake of krypton by the body and its short-and longer-term biological retention after inhalation using Kr⁷⁹.

Twelve male and four female adult volunteer subjects with no known respiratory disorders participated in this study. The subjects ranged in age from 30 to 61 years, and in weight from 124 to 234 pounds. These broad ranges were chosen to determine differences in retention according to age, respiratory volume, and percent body fat. Each of the subjects inhaled 130 to 1,250 microcuries of Kr⁷⁹ gas mixed with normal breathing air during exposures of about 10 minutes, and were then counted in the Brookhaven whole-body counter to determine body retention of Kr⁷⁹ over time.

This study showed that krypton deposited in different body compartments (lungs, muscles, and fatty tissues), each clearing at different rates, with retention half-times ranging from a few seconds to almost 10 hours. Krypton was retained longest in fatty tissues. Longer retention times correlated well with increasing amount of body fat, which acted as a repository in the body for krypton. This research was supported by the U.S. Energy Research and Development Administration.

References

Ellis, K.J., S.H. Cohn, H. Susskind, and H.L. Atkins. AKinetics of Inhaled Krypton in Man.@Health Physics, Vol. 33, 1977, pp. 515B522.  "

BNL-70. Study of Xenon-127 Retention

IN 1976, investigators of the Applied Science and Medical Departments, Brookhaven National Laboratory, studied the total-body retention and clearance of xenon gas using the isotope xenon-127 (Xe¹²⁷). Xenon was used in nuclear medicine clinics in routine studies of lung ventilation and perfusion as an aid to diagnosis of pulmonary disease. The purpose of this study was to determine the uptake of xenon by the body and its short-and longer-term biological retention after inhalation, and how these values are influenced by amount of body fat.

Seven male and five female volunteer subjects with no known pulmonary disease participated in this study. The subjects ranged in age from 29 to 61 years, and in weight from 110 to 306 pounds to determine differences in man according to age, respiratory volume, and percentage body fat. Each of the subjects inhaled up to 100 microcuries of Xe¹²⁷ gas mixed with normal breathing air during exposure periods of 10 to 30 minutes, and were then counted in the Brookhaven whole-body counter to determine body retention of Xe¹²⁷ over time. The subjects then repeated the study at different concentrations of Xe¹²⁷ in breathing air.

This study showed that xenon totally cleared from the body three days after inhalation and that longer retention times correlated well with increasing amounts of body fat, which acted as a repository in the body for xenon gas. The results of this study were used to estimate radiation doses to nuclear medicine patients undergoing diagnostic examinations. This research was supported by the U.S. Energy Research and Development Administration.

References

Susskind, H., H.L. Atkins, S.H. Cohn, K.J. Ellis, and P. Richards. AWhole-Body Retention of Radioxenon.@Journal of Nuclear Medicine, Vol. 18, 1977,  pp. 462B471.  "