List of Experiments

Lawrence Livermore National Laboratory

LLNL-1. In Vivo Calibration Studies Using Humans Administered Niobium-92m, Barium-133, Palladium-103, Chromium-51, and Strontium-85

THE PURPOSE OF these studies was to develop accurate calibration factors forin vivo counting equipment and to cross­calibrate the various U.S. and European counting centers. Volunteer subjects were administered radionuclides at Harwell Laboratory (United Kingdom) and were whole-body or chest counted at the Lawrence Livermore National Laboratory and at other Department of Energy contractor in vivo counting facilities in the United States. Two subjects were from Lawrence Livermore Laboratory and the remainder were from the United Kingdom.

This study was broad in scope and spanned several years. From 1972 to 1976, three males inhaled palladium-103 and chromium-51Blabeled microspheres and were counted in 14 labs in Europe and the United States. From 1979 to 1985, 19 men and women inhaled niobium-92m (Nb^92m)Blabeled microspheres and were counted at several labs. During the 1986 to 1988 period, two males were injected with barium-133; one of the two was also injected with strontium-85. During the 1988 to 1990 period, eight males (including five who earlier had inhaled Nb^92m) were exposed to Nb^92m and counted.

This research was jointly sponsored by the Atomic Energy Research EstablishmentCHarwell, British Nuclear Fuels, the General Electricity Generating Board, the International Atomic Energy Agency, and the U.S. Department of Energy (and its predecessor agencies). (Previously described in #15 on the original list of 48 experiments released by DOE in June 1994; included in The DOE Roadmap of February 1995, and since revised).

References

Anderson, A.L., and G.W. Campbell. LLL Plutonium Lung Counter Calibration and Discussion of Errors. Livermore, CA: Lawrence Livermore National Laboratory, UCRL­78409, June 20, 1976.

Campbell, G.W., A.L. Anderson, F.A. Fry, D. Newton, and D. Ramsden. Calibration of Phoswich Detectors for Assessment of Plutonium in Lungs: The Methods of Four Laboratories Compared. Livermore, CA: Lawrence Livermore Laboratory, UCRL­84516, June 11, 1980.

Dean, P.N., R.V. Griffith, and A.L. Anderson. Design Criteria for Phantoms for Calibration of External Detectors for the In Vivo Assay of Plutonium. Livermore, CA: Lawrence Livermore National Laboratory, UCRL­76411, November 17, 1975.

Newton, D., F.A. Fry, B.T. Taylor, M.C. Eagle, and R.C. Sharma. AIntralaboratory Comparison of Techniques for Measuring Lung Burdens of Low­Energy Photon Emitters.@Health Physics. Vol. 35, 1978, pp. 751B777.

Newton, D., G.W. Campbell, A.L. Anderson, and J.C. Fisher. Consistent X­Ray Counting Efficiencies for Plutonium In Lungs, Derived by Independent Methods. Livermore, CA: Lawrence Livermore Laboratory, UCRL­83946, February 4, 1980.

Swinth, K.L., W.J. Bair, P.N. Dean, J. Rundo, and F.K. Tomlinson. Status and Trends in the External Counting of Inhaled Heavy Elements Deposited In Vivo. Livermore, CA: Lawrence Livermore Laboratory, UCRL­83949, February 5, 1980.  "

LLNL-2. Ozone Effects on Overall and Regional Lung Function Using Nitrogen-13 and Oxygen-15

IN THIS COLLABORATION between the University of Washington, Seattle and Lawrence Livermore National Laboratory, the impact of ozone on the human lungs was studied. The objective was to determine the functional changes that might result from low ozone levels in smog.

Four healthy, male subjects were exposed to 0.4 part per million by volume concentrations of nonradioactive ozone for a total of 2.5 hours. Periods of exercise and rest were alternated during the exposure. The subjects then inhaled small quantities of radioisotope­labeled gas mixtures for the purpose of measuring lung function. The mixtures were similar to air, with an oxygen-to-nitrogen ratio of roughly 1 to 4; however, in the first mixture, a small amount of the nitrogen was a radioactive tracer, nitrogen-13. The second mixture contained a few percent of radioactive oxygen-15Blabeled carbon dioxide.

The results of this test suggested that ozone caused nonuniform mechanical alteration to the central and peripheral airways. The study was performed under a contract from the U.S. Department of Energy from 1977 to 1978 and in part by a grant from the National Heart, Lung, and Blood Institute. (Previously described in #16 on the original list of 48 experiments released by DOE in June 1994; included in The DOE Roadmap of February 1995, and since revised.)

References

Meyer, P. AOzone, Respiration, and the Bends.@Energy and Technology Review. Livermore, CA: Lawrence Livermore Laboratory, UCRL­52000­81­12, December 1981, pp. 22B31.

AOzone Effects on Overall and Regional Lung Function.@Lawrence Livermore National Laboratory Review Board File. Livermore, CA: Lawrence Livermore National Laboratory, B361 Rm. B940A, Institutional Review Board, IRB Protocol File, Active GrantsCCollaborative, University of Washington Ozone Effect on Overall Lung Function.  "

LLNL-3. Decompression Sickness Studies Using Nitrogen-13 and Argon-41

THE LAWRENCE LIVERMORE NATIONAL LABORATORY and the U.S. Navy conducted studies during the 1980s using the radionuclide tracers nitrogen-13 (N¹³) and argon-41 (Ar⁴¹) to acquire information on the uptake and clearance of nitrogen gas in man. This research was performed to better understand decompression sickness of deep­sea divers; such sickness is thought to result from excessive accumulation of nitrogen in divers=bodies.

In these studies, a total of 11 healthy subjects (Navy volunteers) breathed air containing N¹³; 2 of the 11 also breathed air containing Ar⁴¹ tracers. Each subject was monitored using gamma detectors to determine the concentration and location of the radioactive tracers contained in the subject=s body as a function of time after uptake. The amounts of N¹³ and Ar⁴¹ inhaled depended on the amounts breathed by the subjects. This air contained a few millicuries of N¹³ and a few dozen microcuries of Ar⁴¹ per liter of breathing air. Absorbed doses to subjects were estimated to be about 0.3 to 0.5 rad to the lungs and trachea and 0.01 rad to the whole body.

This work was supported by the Naval Medical Research Institute and the U.S. Department of Energy. (Previously described in #14 on the original list of 48 experiments released by DOE in June 1994; included in The DOE Roadmap of February 1995, and since revised)

References

Meyer, P. AOzone, Respiration, and the Bends.@Energy and Technology Review. Livermore, CA: Lawrence Livermore National Laboratory, UCRL­52000­81­12, December 1981, pp. 22B31.

Weathersby, P.K., P. Meyer, E.T. Flynn, L.D. Homer, and S. Survanshi. ANitrogen Gas Exchange in the Human Knee.@Journal of Applied Physiology. Vol. 61, No. 4, October 1986, pp. 1,534B1,545.  "

Los Alamos National Laboratory

LANL-1. Tritium Studies at Los Alamos Scientific Laboratory

DURING THE EARLY 1950s, Los Alamos Scientific Laboratory conducted studies on the human uptake, distribution, and retention of tritium (H³). Three volunteers, all researchers working on the studies, participated as subjects. In one experiment, a male subject immersed his arm up to the elbow in water containing 0.1 millicurie of tritium per milliliter. This study showed that the rate of absorption through the skin was too slow to pose a hazard. The whole body would have to be immersed for more than 1 hour before the U.S. Atomic Energy Commission-recommended exposure limit was reached.

In another study, all three subjects inhaled for 4 to 5 minutes oxygen that was saturated with tritium water vapor (HTO) which, when condensed, contained 1.16 millicuries of tritium per milliliter of water. Results showed that 98 to 99 percent of the tritium was retained in the body after inhalation.

In a third study, the three subjects drank water containing tritium. Water volumes ranged from 100 to 1,000 milliliters (.33 to 4 cups) and level of activity ranged from 1,640 to 2,920 microcuries.

These studies showed that water absorption from the gastrointestinal tract begins 2 to 9 minutes after ingestion, that absorption is a linear function of time, and that absorption is proportional to the amount ingested. All these studies were used to establish standards for occupational exposure to tritium. This work was supported by the U.S. Atomic Energy Commission. (These experiments were referenced in the Markey report and included in The DOE Roadmap of February 1995)

References

Pinson, E.A. The Body Absorption, Distribution, and Excretion of Tritium in Man and Animals. Los Alamos, NM: Los Alamos Scientific Laboratory, LA­1218, March 12, 1951.

Pinson, E.A. Lung Absorption of HTO by Man Upon Inspiration of HTO Water Vapor. Los Alamos, NM: Los Alamos Scientific Laboratory, LA­1465, June 1952.

Pinson, E.A. The Body Absorption of Ingested Tritium Water and the Water Dilution Volume of Man. Los Alamos, NM: Los Alamos Scientific Laboratory, LA­1464, June 1952.  "

LANL-2. Metabolism of EDTA in Humans Using Carbon-14

IN 1953, Los Alamos Scientific Laboratory conducted studies on the human metabolism of the chelating agent ethylenediaminetetraacetic acid (EDTA) labeled with carbon­14 (C¹⁴). The purpose was to gain information that would help establish optimum dosage schedules and identify any harmful effects.

Twelve young healthy men served as subjects in four groups of three. One group was administered an intravenous injection of 2.2 milligrams of C¹⁴­labeled EDTA; the second received an intramuscular injection of 2.2 milligrams; the third received oral administration of 1.5 milligrams; and the fourth group had 2.0 milligrams applied directly to the skin.

The studies showed that EDTA passed through the body essentially unchanged and that it was excreted primarily by the kidney within 1 hour of intravenous injection and 1.5 hours after intramuscular injection. EDTA is poorly absorbed in the gastrointestinal tract and practically not at all through the skin. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #43 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Foreman, H., and T.T. Trujillo. AThe Metabolism of C¹⁴ Labeled Ethylenediaminetetraacetic Acid in Human Beings.@The Journal of Laboratory and Clinical Medicine. Vol. 43, No. 4, pp. 566B571.

Biomedical Research Group of the Health Division Annual Report 1953. Los Alamos, NM: Los Alamos Scientific Laboratory, LA­1690, 1954, p. 17.  "

LANL-3. Radiation Exposure of Aircrews in Mushroom Clouds

DURING THE 1955 TEAPOT and the 1956 REDWING nuclear test series, manned aircraft were used to map the amount and distribution of radiation within some of the resulting Amushroom@clouds. The objective was to obtain information needed to plan for the safe and effective use of military aircraft in cloud areas during combat operations.

Studies conducted in 1953 using animal subjects in drone aircraft had previously shown that it would be safe for manned aircraft to enter atomic clouds relatively soon after detonation. Penetrations of clouds from low­yield detonations were made during Operation TEAPOT in 1955. Penetrations of the larger clouds from high­yield detonations were made during Operation REDWING in 1956. Special radiation exposure limits, in excess of the usual 3.9 roentgens maximum permissible exposure limit, were established for some of these flight crews.

During Operation TEAPOT, four Air Force officers were permitted to receive up to 15 roentgens, and two received this amount. Exposures of up to 25 roentgens were permitted during Operation REDWING, but no one received this amount. The largest exposures were approximately 15 roentgens for three officers.

Pre­ and post-mission urine tests and evaluation in whole-body counters showed no significant internal deposition of fission products or unfissioned plutonium. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995)

References

Headquarters Field Command. AEarly Cloud Penetrations.@Report of Operation REDWING Project 2.66a. Armed Forces Special Weapons Center, WT­1320. Reynolds Electrical and Engineering Co., Inc., Coordination and Information Center, Las Vegas, NV, CIC Document 68117.

Headquarters Field Command. AManned Penetration of Atomic Clouds.@Report of Operation TEAPOT Project 2.8a. Armed Forces Special Weapons Center, WT­1156. Reynolds Electrical and Engineering Co., Inc., Coordination and Information Center, Las Vegas, NV, CIC Document 12800.

Headquarters Field Command. AThe Radiation Hazards to Personnel Within an Atomic Cloud.@Report of Operation UPSHOT/KNOTHOLE Project 4.1.Armed Forces Special Weapons Center, WT­743. Reynolds Electrical and Engineering Co., Inc., Coordination and Information Center, Las Vegas, NV, CIC Document 40992.  "

LANL-4. Determination of the Survival Time of Red Blood Cells by Chromium-51 Labeling

A STUDY WAS CONDUCTED by Los Alamos Scientific Laboratory in 1957 to determine the survival times of circulating red blood cells in healthy and diseased subjects. Thirty­two subjects (7 healthy and 25 diseased) received intravenous injection of samples of their own red blood cells that had been previously removed and tagged with radioactive chromium­51.

After tagging, the red cells were injected back into the donor, and the person=s uptake and radioactivity were assessed in the whole-body counter. Half­times for the survival of the chromium tag were determined. Large volumes of urine were also obtained from the subjects and counted to determine excretion rates. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #26 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

AApplication of Low Level In Vivo Counting Techniques to Clinical Investigations.@Annual Report of the Health Division 1957. Los Alamos, NM: Los Alamos Scientific Laboratory, LA-2216, pp. 62B63.  "

LANL-5. Studies of the Metabolism and Excretion of Alkali Metal Radionuclides in Humans

SCIENTISTS AT THE Los Alamos Scientific Laboratory conducted a series of studies to determine the metabolism and excretion of alkali metals as part of a general research program on the retention, excretion, and absorption of radioactive materials in humans.

Sodium­22, potassium­42, and rubidium­86 were administered orally to 10 normal, healthy subjects and were measured at various times thereafter in the whole-body counter. The distribution and retention patterns for these materials were determined periodically for about 1 year. Radiocesium was also administered and measured. These experiments are described separately, under LANL­8. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #25 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Richmond, C.R. ARetention and Excretion of Radionuclides of the Alkali Metals by Five Mammalian Species.@Biological and Medical Research Group of the Health Division Semiannual Report JulyBDecember 1959. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2445, 1960, pp. 71B79.  "

LANL-6. Absorption and Retention of Orally Administered Iron-59 in Humans

THIS STUDY WAS conducted at Los Alamos Scientific Laboratory in 1959. The purpose was to determine the absorption and retention of orally administered iron in subjects. A second objective was to evaluate the whole-body counting technique and equipment as a tool for measuring iron in the human body.

Sixty­six subjects were part of this test, including one pregnant woman and four children. Also included in the study were hospital patients with anemia, leukemia, or polycythemia rubra vera. Each of the study participants ingested 0.5 to 0.7 microcurie of iron­59 as ferrous citrate in water. The oral dose was followed with an additional 100 to 200 milliliters of tap water to wash the radioactive iron into the stomach. Body counting and fecal bioassay were used to determine the relationship between ingested, retained, and excreted iron.

The study showed that there was an apparent lack of iron absorption with leukemia and infection. Also, the pregnant woman absorbed larger amounts of iron. This study was supported by the U.S. Atomic Energy Commission. (Previously described in #40 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Lushbaugh, C.C., and D.B. Hale. AClinical Applications of Whole-Body Counting: A Clinical Comparison of the Absorbability of Ferrous versus Ferric Salts in Normal Human Subjects.@Biological and Medical Research Group of the Health Division Semiannual Report JulyBDecember 1959. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2445, 1960, pp. 337B347.

Lushbaugh, C.C., and D.B. Hale. ADetermination of Absorbability of Oral Radioiron in Health and Disease in Man by Whole-Body Scintillometry.@In Radioactivity in Man Symposium. Chicago, 1962. pp. 417B429.  "

LANL-7. Determining Thyroid Uptake and Retention of Iodine-131

IN 1959, Los Alamos Scientific Laboratory conducted studies on whole-body measurement techniques for determining thyroid uptake of iodine­131 (I¹³¹).

Seventeen normal subjects or patients, both men and women, ranging in age from 10 to 57, drank water solutions containing 1.5 to 3.0 microcuries of I¹³¹ as sodium iodide. Study results showed that the whole-body liquid scintillation measurement technique together with a 3x3-inch collimated sodium iodide thyroid probe, provided a simple, valid means of determining whole-body iodide retention, thyroid uptake, and thyroid function.

Additional studies were conducted to address how thyroid retention changed with disease, chemotherapy, and metabolic status. These studies involved some of the same patients, but also added others. Six children whose thyroid gland had been removed were added, as was one patient with an overactive thyroid and another with an underactive thyroid. A total of 63 patients were administered I¹³¹ either orally or intravenously.

These studies showed that retention rates in diseased patients varied widely from normal rates, and that retention of I¹³¹ was influenced by therapy. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #45 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995 and since revised.)

References

Lushbaugh, C.C., and D.B. Hale. AClinical Applications of Whole-Body Scintillometry. III. Whole-Body Retention of Iodine­131 as a Method of Studying Thyroid Function in Man.@Biological and Medical Research Group of the Health Division Semiannual Report JulyBDecember 1959. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2445, 1960, pp. 361B373.

Lushbaugh, C.C., and P.S. New. AClinical Applications of Whole-Body Scintillometry. II. A Comparison of Three Different Methods of Determining Retention and Thyroid Uptake of Orally Administered I¹³¹.@Biological and Medical Research Group of the Health Division Semiannual Report JulyBDecember 1959. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2445, 1960, pp. 348B360.  "

LANL-8. Long-Term Retention of Cesium­134 and Cesium-137 in Humans

FROMAPPROXIMATELY 1959 to 1961 , a study was conducted at the Los Alamos Scientific Laboratory on the long­term retention of radioactive cesium in humans. Four healthy, adult males participated in this study.

Two of the subjects received oral doses of 1 and 1.4 microcuries of cesium­134 (Cs¹³⁴)as cesium chloride. The subjects were followed by whole-body counting for 106 and 910 days, respectively, to determine the gastrointestinal tract uptake and whole-body. The other two subjects were administered about 1 microcurie of cesium-137 (Cs¹³⁷) and were followed by whole-body counting for about 500 days.

This study showed that the biological retention half­time of cesium in humans was about 137 days. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #25 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Richmond, C.R., J.E. Furchner, and W.H. Langham. ALong­Term Retention of Radiocesium by Man.@Biological and Medical Research Group of the Health Division Semiannual Report JanuaryBJune 1961. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2627, 1961, pp. 163B174.  "

LANL-9. Study of the Retention and Excretion of Iodine-131

IN 1960, a study was performed at Los Alamos Scientific Laboratory to determine the retention and excretion of iodine­131 (I¹³¹). Twenty­six normal subjects, including 17 women, 3 men, 3 girls, and 3 boys participated in the study. Each volunteer was given an oral dose of liquid containing 8 microcuries of I¹³¹ as sodium iodide, and then measured for whole-body and thyroid content of I¹³¹ within 1 hour. Additional measurements were made on the 1st, 2nd, 3rd, 4th, 7th, 10th, 14th, and 18th days following the ingestion.

This study showed that approximately 20 percent of the ingested I¹³¹ was taken up by the thyroid gland, and the remaining 80 percent was excreted in the urine by the kidneys. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #19 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Lushbaugh, C.C., D.B. Hale, and C.R. Richmond. AClinical Applications of Whole-Body Scintillometry. IV. Turnover Rate of Protein­Bound Iodide.@Biological and Medical Research Group of the Health Division Semiannual Report JanuaryBJune 1960. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2455, 1960, pp. 364B371.  "

LANL-10. Absorption and Uptake of Iodine-131 and Sodium-24 in Humans

IN 1960, an experiment was conducted at Los Alamos Scientific Laboratory to determine the feasibility of in vivo measurements to study the absorption of radionuclides through the skin.

Liquid solutions of 10 microcuries of sodium­24 (Na²⁴) or 51 microcuries of iodine­131 (I¹³¹) were placed on the palms of two volunteer subjects employed at the Laboratory. After allowing absorption to occur, the palms were washed and the subjects were counted periodically in the Laboratory=s whole-body counter to determine the fraction of either radionuclide absorbed through the skin.

In a second experiment, two volunteer subjects ingested 0.18 microcurie of Na²⁴ or 0.14 microcurie of I¹³¹ to determine the gastrointestinal absorption and whole-body retention of these radionuclides. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #27 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Van Dilla, M.A., C.R. Richmond, and J.E. Furchner. ACutaneous Absorption by Human Subjects, I. Studies with Sodium­24 and Iodine­131.@Biological and Medical Research Group of the Health Division Semiannual Report JulyBDecember 1960. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2526, 1961, pp. 164B171. "

LANL-11 Retention of Iodine-131 in Subjects with Inflammatory Liver Disease

IN 1960, A STUDY was conducted at Los Alamos Scientific National Laboratory on the use of an iodine­131 (I¹³¹)Blabeled blood dye in determining liver function.

Ten normal subjects and 18 persons suffering from inflammatory hepatic disease were injected intravenously with 10 microcuries of I¹³¹­labeled dye (rose bengal). The time/activity curves for retention of I¹³¹ in the bloodstream were determined, using the Los Alamos arm counter.

The blood retention curve was found to be a better measurement of liver function than the clearance rate of labeled rose bengal dye measured in urine. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #28 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Lushbaugh, C.C., D.B. Hale, and R. McGill. AThe Use of the Arm Counter to Determine the Degree of Hepatic Function.@Biological and Medical Research Group of the Health Division, Semiannual Report JanuaryBJune 1960. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2455, 1960, pp. 223B229.  "

LANL-12. Gastrointestinal Passage of Radioactive Particles Containing Manganese-54 and Uranium-235

IN THE EARLY 1960s, Los Alamos Scientific Laboratory conducted studies on the passage of radioactive particles through the human gastrointestinal tract. These studies addressed the issue of reentry and destruction of nuclear­powered space vehicles in the earth=s atmosphere and subsequent ingestion of the resulting airborne particles by humans.

Fifty­seven normal adults participated. Each subject swallowed a gelatin capsule containing three radioactive particles. One particle was ceramic, about 150 microns in diameter, and contained approximately 150 picocuries of manganese­54. The other two particles were uranium carbide, about 175 microns in diameter, and contained an unspecified amount of uranium­235 activity. The total calculated radiation dose delivered to the gastrointestinal tract in these studies was extremely lowCwell below the maximum permissible level for these materials. Several subjects repeated the ingestion at different times of day to estimate the time­of­day variations. One subject repeated the test 10 different times to estimate the variation within a single individual.

The studies showed that particle density did not influence passage rate and that there was no significant holdup of particles in the digestive system. Transit times corresponded to individual bowel movement characteristics. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Some Biological Aspects of Radioactive Microspheres. Los Alamos, NM: Biological and Medical Research Group, Los Alamos Scientific Laboratory, LA­3365­MS, June 20, 1965.  "

LANL-13. Metabolism of Zinc-65 in Human Leukemia

A STUDY WAS CONDUCTED at Los Alamos Scientific Laboratory in early 1961 on the metabolism of zinc­65 (Zn⁶⁵) in human cancer patients with chronic leukemia. This experiment involved a single subject. A 15­year­old female patient with chronic myelogenous leukemia was given an oral dose of 0.6 microcurie of zinc­65 (Zn⁶⁵) as zinc chloride 137 days prior to death. One hour after administration and on days 1, 2, 3, 20, and 137 the subject was studied for whole-body Zn⁶⁵ in the Los Alamos human counter. In addition, tissue samples were removed at autopsy and sampled for Zn⁶⁵.

The findings of this study showed that Zn⁶⁵ was retained less tenaciously by the leukemia patient than by previously studied normal subjects. (See LANL-15.) This work was supported by the U.S. Atomic Energy Commission. (Previously described in #32 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Furchner, J.E., C.R. Richmond, and G.A. Trafton. AMetabolism of Zinc­65 in Humans.@Biological and Medical Research Group of the Health Division Annual Report July 1961BJuly 1962. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2780, 1962, pp. 66B77.

Furchner, J.E., and C.R. Richmond. AEffect of Dietary Zinc on the Absorption of Orally Administered Zn⁶⁵.@Health Physics. Vol. 8, 1962, pp. 35B40.

Richmond, C.R., J.E. Furchner, and G.A. Trafton. ALong-Term Retention of Zinc­65 by Man.@Biological and Medical Research Group of the Health Division Semiannual Report JulyBDecember 1960. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2526, 1961, pp. 15B20.

Richmond, C.R., C.C. Lushbaugh, M.W. Rowe, and M.A. Van Dilla. AMetabolism of Zinc­65 in a Terminal Leukemia Case.@Biological and Medical Research Group of the Health Division Semiannual Report JanuaryBJune 1961. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2627, 1960, pp. 263B269.

Richmond, C.R., J.E. Furchner, G.A. Trafton, and W.H. Langham. AComparative Metabolism of Radionuclides in Mammals­I: Uptake and Retention of Orally Administered Zn⁶⁵ by Four Mammalian Species.@Health Physics. Vol. 8, 1962, pp. 481B489.  "

LANL-14. Iodine-131 Used to Determine Thyroid Uptake Measurement Techniques

IN 1961, Los Alamos Scientific Laboratory conducted studies intended to improve the accuracy of whole-body counting techniques for determining thyroid uptakes. Previous experience had shown that body mass influenced overall absorption and affected the accuracy of thyroid uptake measurements.

An unspecified number of subjects received oral administration of 8 microcuries of iodine­131. A Amock iodine@mixture of barium­133 and cesium­134 equal to 2.48 microcuries was also administered to establish a control standard.

The results of these studies were used to establish normal human absorption values for men, women, and children of various ages. (Previously described in #45 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Lushbaugh, C.C. AProgress in Refinement of the Whole-Body Counting Technique for Determining Thyroid Uptake.@Biological and Medical Research Group of the Health Division Semiannual Report JanuaryBJune 1961. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2627, 1961, pp. 291B297.  "

LANL-15. Uptake and Retention of Zinc­65

DURING 1961 AND 1962, a study was conducted at Los Alamos Scientific Laboratory on the uptake and retention of radioactive materials by subjects. Three males and one female between the ages of 29 and 48 received a single oral dose of 0.6 to 1.0 microcurie of zinc chloride in water. The subjects were evaluated for whole-body distribution and retention of zinc-65 (Zn⁶⁵) with time. These measurements were made in the Los Alamos whole-body center. Urine and feces were also obtained and analyzed for Zn⁶⁵. Measurements continued 416 to 664 days after the administration of Zn⁶⁵. These data were used to determine the retention and excretion of Zn⁶⁵ in men and women for comparison with other animal species. This study was supported by the U.S. Atomic Energy Commission. (Previously described in #32 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Richmond, C.R., J.E. Furchner, G.A. Trafton, and W.H. Langham. AComparative Metabolism of Radionuclides in Mammals: I. Uptake and Retention of Orally Administered Zn⁶⁵ by Four Mammalian Species.@Health Physics. Vol. 8, 1962, pp. 481B489.  "

LANL-16. Iron-59 Absorption in Normal Human Subjects

FROM MID-1961TO MID­1962, a study was conducted at the Los Alamos Scientific Laboratory on the absorption of iron by normal subjects. The objective of the study was to determine whether the ferrous or ferric form was more readily absorbed.

A group of volunteers composed of 20 normal men and 30 normal women was included in the study. The subjects were divided randomly into two subgroups. Each subject received 0.27 microcurie of iron orally. Some received the iron in the form of ferrous citrate labeled with iron­59 (Fe⁵⁹). The others received the iron in the form of ferric chloride labeled with Fe⁵⁹. A whole-body count was performed immediately after ingestion and again 7 days later. At the time of the second body count, blood samples were drawn and characterized.

No difference was found in human uptake between the ferrous and ferric forms of iron. This study was supported by the U.S. Atomic Energy Commission. (Previously described in #40 on the original list of 48 experiments released by DOE in June 1994)

References

Lushbaugh, C.C., and D.B. Hale. AClinical Applications of Whole-Body Scintillometry I. Retention of Orally Administered Iron.@Biological and Medical Research Group of the Health Division Semiannual Report JulyBDecember 1959. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2445, 1960, pp. 337B347.

Lushbaugh, C.C., and D.B. Hale. ADetermination of Absorbability of Oral Radioiron in Health and Disease in Man by Whole-Body Scintillometry.@In Radioactivity in Man Symposium. Chicago, 1962, pp. 417B429.  "

LANL-17. Cutaneous Absorption of Strontium-85

FROM 1961 TO 1962, Los Alamos Scientific Laboratory conducted studies on the absorption of strontium­85 (Sr⁸⁵) through human skin. Radioactive strontium chloride was applied in a gauze patch to the forearm of two subjects and held in place with adhesive tape. The amount of Sr⁸⁵ administered was about 70 microcuries. After 2 days, one subject had absorbed 0.2 percent and the other had absorbed 0.6 percent.

The study showed that absorption through the skin occurred, but at very low levels. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #44 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Van Dilla, M.A., C.R. Richmond, J.E. Furchner, and M.W. Rowe. ACutaneous Absorption of Radionuclides by Human Subjects. II. Strontium­85.@Biological and Medical Research Group of the Health Division Annual Report July 1961BJune 1962. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2780, 1962, pp. 154B157.  "

LANL-18. Retention of Strontium-85

FROM 1961 TO 1962, Los Alamos Scientific Laboratory conducted studies on the whole-body retention of strontium­85 (Sr⁸⁵) in humans. Three male laboratory employees ingested 1.07 microcuries of Sr⁸⁵ in 100 milliliters of tap water.

The studies showed that Sr⁸⁵, with its 65­day half­life, is suitable for studying short­term retention of fallout but not appropriate for long­term retention studies. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #44 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Furchner, J.E., M.A. Van Dilla, M.W. Rowe, and C.R. Richmond. ARetention of Strontium­85 by Man.@Biological and Medical Research Group of the Health Division Annual Report July 1961BJune 1962. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2780, 1962, pp. 43B49. "

LANL-19. Studies on the Retention of Iodine­131 in Humans

FROM 1961 TO 1962, Los Alamos Scientific Laboratory conducted studies on the retention of radioiodinated para-toluidine polyvinyl-pyrrolidone, also known as PVP-I¹³¹. The purpose of the study was to determine whether PVP­I¹³¹ could be used to detect the presence of vascular leaks into the gastrointestinal or renal excretory tracts.

Eight adults were injected intravenously with 0.7 microcurie of PVP­I¹³¹. Four of the subjects had medical conditions that included known internal bleeding. The study showed that the bleeding subjects lost the iodine more rapidly than the nonbleeding subjectsCin one case, almost twice as fastCindicating that PVP­I¹³¹ was an effective detector of internal bleeding.

In a related study, one of these subjects drank a water solution containing 0.06 microcurie of PVP­I¹³¹ to determine retention in the thyroid gland. The study showed little retention, indicating that PVP­I¹³¹ is not readily absorbed. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #45 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Lushbaugh, C.C., and D.B. Hale. AClinical Applications of Whole-Body Counting: Retention of Raovin Iodine­131 as a Measure of Serum or Blood Loss.@Biological and Medical Research Group of the Health Division Annual Report July 1961BJune 1962. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­2780, 1962, pp. 188B193.  "

LANL-20. Thyroid Function Studies Using Sodium Iodide-131

FROM 1961 TO 1962, Los Alamos Scientific Laboratory conducted studies on human thyroid function using iodine­131 (I¹³¹) administered as sodium iodide. At least two adult females received 0.5 microcurie by oral administration. Tests were repeated several times in combination with various drugs and uptakes were measured and compared.

These studies showed which drug therapies were most effective in treating thyroid disorders. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #45 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Lushbaugh, C.C., and D.B. Hale. AClinical Applications of Whole-Body Counting: Determination of Thyroidal Activity from Sodium Iodine­131 Retention Measurements with Humco II.@Biological and Medical Research Group of the Health Division Annual Report July 1961BJune 1962. Los Alamos, NM: Los Alamos National Laboratory, LAMS­2780, 1962, pp. 181B187.  "

LANL-21.

(Essentially a duplicate of LANL-15 in The DOE Roadmap)

LANL-22. Cesium-132 Metabolism in Humans

FROM 1962 TO 1963, a study was conducted at Los Alamos Scientific Laboratory to determine the retention and excretion of cesium­132 (Cs¹³²) in humans. The subjects were three male and one female normal, young adults in good health. These subjects were injected intravenously with 0.65 microcurie of Cs¹³² as cesium chloride. Three of the subjects were counted approximately 30 times over a 45­day period. Whole-body retention of Cs¹³² was determined by measurements of the subjects in the Laboratory=s whole-body counters. This research was supported by the U.S. Atomic Energy Commission. (Previously described in #25 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Richmond, C.R., J.E. London, and J.E. Furchner. ARetention of Intravenously Administered Cesium­132 by Man.@Biological and Medical Research Group of the Health Division Annual Report July 1962BJune 1963. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS­3034, 1963, pp. 21B33.  "

LANL-23. Thyroid Studies Using Small Amounts of Iodine-125 and Iodine-131

IN APPROXIMATELY 1963 , Los Alamos Scientific Laboratory conducted studies on thyroid metabolism, using very small amounts of iodine­125 (I¹²⁵) and iodine­131 (I¹³¹). The purpose was to determine the retention of iodine in the thyroid as a function of time, with a particular interest in radioiodine metabolism in children. Nineteen normal male and female subjects ranging in age from 4 to 46 drank approximately 10 nanocuries each of I¹²⁵ and I¹³¹ mixed together in water.

Subsequent measurements showed that there was little difference in radioiodine metabolism between children and adults. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #45 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Van Dilla, M.A., and M.J. Fulwyler. AThyroid Metabolism in Children and Adults Using Very Small (Nanocurie) Doses of Iodine­125 and Iodine­131.@Health Physics. Vol. 9, 1963, pp. 1,325B1,331.

Van Dilla, M.A., and M.J. Fulwyler. ARadioiodine Metabolism in Children and Adults After the Ingestion of Very Small Doses.@Science. Vol. 144, No. 3614, April 1964, pp.178B179.  "

 ‡  ‡  ‡

LANL-24. Studies of the Metabolism of Antituberculous Drugs Using a Carbon-14 Tracer

IN 1959, Los Alamos Scientific Laboratory scientists collaborated with physicians at the Department of Public Health and Preventive Medicine, Cornell University, New York Hospital Medical Center on a series of studies on the effects of certain drugs on the metabolism of isoniazid, a drug for treatment of tuberculosis.

Of the seven study subjects, five (four males and one female, ages 25 to 80 years) were Navajo Indian patients in the U.S. Public Health Service Hospital at Fort Defiance, Arizona. Two of the males were nontubercular and had no prior history of isoniazid therapy. Two other subjects (one white, age 52 years, and one Hispanic, age 36 years) were tuberculosis patients in the Los Alamos Medical Center.

Intramuscular injections of 186 to 327 microcuries carbon-14 (C¹⁴)Blabeled isoniazid chloride, followed by at least 100 milligrams of unlabeled isoniazid were administered to each subject. Four subjects received one or two repeat injections of C¹⁴-labeled isoniazid at intervals of up to 5 weeks in combination with streptomycin and oral para-aminosalicylic acid (PAS). Two of these subjects also received oral pyridoxine.

These studies showed that labeled isoniazid was rapidly excreted in the urine (up to 95 percent in the first 24 hours). The metabolic products of isoniazid were found to be acetylisoniazid and isonicotinic acid. Neither pyridoxine nor PAS had an appreciable effect on isoniazid plasma turnover time or on urinary excretion rate. This work was supported by the U.S. Atomic Energy Commission, and in part by grants from the Navajo Tribal Council, the American Thoracic Society, and the U.S. Public Health Service.

References

Boone, I.U., L.M. Conklin, G. Trafton, and R. Des Pres. AMetabolism of C¹⁴ in Humans.@Biological and Medical Research Group (H-4) of the Health Division Semiannual Report JulyBDecember 1959. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS-2445, 1960, pp. 326B328.

Boone, I.U., A. Murray, and R. Des Pres. Metabolism of C¹⁴-Isoniazid in Humans. Los Alamos, NM: Los Alamos Scientific Laboratory, LA-2420, 1960.

Des Pres, R., and I.U. Boone. AMetabolism of C¹⁴-Isoniazid in Humans.@American Review of Respiratory Diseases. Vol. 84, No. 1, July 1961, pp. 42B51.

Memorandum. I.U. Boone to T.L. Shipman. December 11, 1958. Los Alamos National Laboratory Health Division Central Administrative Records, Collection TR-6704, Box G36208, Folder AHuman Studies.@  "

LANL-25. Clinical Applications of Whole-Body Scintillometry for Determining Cobalt-60 B Labeled Vitamin B₁₂ Absorption and Retention

STUDIES WERE CONDUCTED in 1961 at the Los Alamos Scientific Laboratory to determine the absorption and retention of vitamin B₁₂ labeled with cobalt-60 (Co⁶⁰) in humans. Because of observed problems in the collection and measurement of excreta, the purpose of these studies was to determine the metabolism and turnover rate of vitamin B₁₂ using the whole-body counter.

The subjects in this study were three healthy people and one patient with severe degenerative disease of the posterio-lateral columns of the spinal cord. Each subject was given 0.5 microcurie of Co⁶⁰-vitamin B₁₂ orally. One hour after ingestion, each subject was given 1,000 micrograms of unlabeled vitamin B₁₂ intramuscularly as a flushing dose. Each subject was then counted daily in the whole-body counter (HUMCO I) for the first week after ingestion and at frequent intervals throughout the following month.

The results of this study showed that the malabsorption of Co⁶⁰-vitamin B₁₂ was easily measured using whole-body counting techniques. This work was supported by the U.S. Atomic Energy Commission.

References

Lushbaugh, C.C., and D.B. Hale AClinical Applications of Whole-Body Scintillometry. VI. Determination of Cobalt-60-Vitamin B₁₂ Absorption and Retention.@Biological and Medical Research Group of the Health Division Semiannual Report JanuaryBJune 1961. Los Alamos, NM: Los Alamos Scientific Laboratory, LAMS-2627, 1961, pp. 280B283.  "

Oak Ridge Sites

OR-1. Early Gallium-72 Studies in Nuclear Medicine

STARTING IN ABOUT 1950, the Oak Ridge Institute of Nuclear Studies (ORINS) conducted studies on the potential therapeutic uses of gallium­72 (Ga⁷²) in human subjects. Previous animal experiments at ORINS indicated that Ga⁷² might be effective in the treatment of bone tumors. Therefore, patients with various kinds of malignant bone tumors were studied with Ga⁷².

Two types of studies were conducted among male and female patients referred to ORINS in 1950 and 1951; most of these 54 patients had late-stage (terminal) disease that was not amenable to surgery or external irradiation therapy.

In one study, 50 to 100 millicuries of Ga⁷² were administered intravenously to 21 patients with some hope of therapeutic benefit. In the other study, lesser amounts (10 to 50 millicuries) of Ga⁷² were administered to 34 other, similar patients, to determine the metabolism and biodistribution patterns of intravenously administered Ga⁷² in man. Several adverse reactions, typical of radiation toxicity, were observed in patients receiving greater than 50 millicuries of Ga⁷².

These studies indicated that Ga⁷² was not suitable for therapy of bone tumors. As a result, subsequent studies focused on other isotopes, such as Ga⁶⁷ or Ga⁶⁸. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised.)

References

Brucer, G.M., G.A. Andrews, and H.D. Bruner. AA Study of Gallium.@Radiology. Vol. 61, No. 4, 1954, pp. 534B613.

AGallium.@Medical Division Annual Report June 1951. Oak Ridge, TN: Oak Ridge Institute of Nuclear Studies, pp. 16B20. Oak Ridge Institute of Nuclear Studies, ORAU Medical Science Division, Vance Road Facility, Room 202A, ORAU­30022.  "

OR-2. Colloidal Gold-198 Studies at Oak Ridge

IN THE 1950s, colloidal gold-198 was studied at the Oak Ridge Institute of Nuclear Studies for potential diagnostic and therapeutic applications in nuclear medicine. Colloidal gold­198 (Au¹⁹⁸) was administered intravenously in a therapeutic trial to terminally ill cancer patients to determine its metabolism and biodistribution.

More than 44 male and female patients with different types of cancer, including 6 with liver cancer and 8 with leukemia, were included in this study between 1949 and 1953. Gold­198 was administered in various amounts over the course of the patient=s disease in the hope of demonstrating a therapeutic effect. In addition, activities of 2.3 to 33.0 millicuries were administered just prior to death to enhance the isotope concentrations in tissues and to study the biodistribution at time of autopsy. Gold Au¹⁹⁸ was also administered by intracavitary injection to treat patients with cancer-related accumulations of fluid in the chest or abdominal cavities. This treatment resulted in the relief of symptoms in some cases.

These studies were conducted after earlier animal studies indicated that this agent had potential therapeutic benefit for patients with certain malignant diseases. Data on the metabolism, distribution, and effects of radiation associated with colloidal Au¹⁹⁸ were compiled during the course of these experimental treatments, and at autopsy, in some cases.

The results of these trials indicated that intracavitary injection of colloidal Au¹⁹⁸ was effective in relieving some of the symptoms of cancer-related fluid accumulations, but that Au¹⁹⁸ colloid showed little promise for therapeutic benefit in patients with liver tumors. These studies were supported by the U.S. Atomic Energy Commission. (Previously described in #12 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995, and since revised)

References

Andrews, G.A., Root, S.W., Kerman, H.D., and Bigelow, R.R. AIntracavitary Colloidal Radiogold in the Treatment of Effusions Caused by Malignant Neoplasms.@Annals of Surgery. Vol. 137, No. 3, March 1953, pp. 375B381.

Andrews, G.A., and Tyor, M.P. AEarly Results of the Treatment of Chronic Granulocytic Leukemia with Intravenous Colloidal Gold-198.@The Journal of Laboratory and Clinical Medicine. Vol. 42, 1953, pp. 777B778.

Kniseley, R.M., and G.A. Andrews. APathological Changes Following Intracavitary Therapy With Colloidal Au¹⁹⁸.@Cancer. Vol. 6, No. 2, March 1953, pp. 303B312.

Root, S.W., G.A. Andrews, R.M. Kniseley, and M.P. Tyor. AThe Distribution and Radiation Effects of Intravenously Administered Colloidal Au¹⁹⁸ in Man.@Cancer. Vol. 7, No. 5, September 1954, pp. 856B866.  "

OR-3. Use of Serum Albumin Labeled with Iodine-131

IN THE EARLY 1950s, the Oak Ridge Institute for Nuclear Studies conducted experiments on the transfer of labeled serum albumin between the peritoneal cavity (within the abdominal cavity) and the blood vessels.

Eleven women hospitalized for ascites (accumulation of fluid in the peritoneal cavity) were the subjects of this study; nine had abdominal carcinomatosis and two had cirrhosis of the liver. These patients were administered intraperitoneally or intravenously with human serum albumin labeled with 200 to 300 microcuries of iodine­131 (I¹³¹). Samples of ascitic fluid and blood were analyzed for I¹³¹­labeled human serum albumin content.

The results showed complete equilibrium of the injected tagged albumin between compartments, and that a similar mechanism was involved in the accumulation of ascitic fluid in the two diseases studied. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Tyor, M.P. AHuman Serum Albumin Tagged with Iodine­131 in Patients With Ascites Caused by Abdominal Carcinomatosis and Portal Cirrhosis: The Rates of Interchange Between the Vascular Compartment and Peritoneal Cavity.@Journal of Laboratory and Clinical Medicine. Vol. 44, No. 1, July 1954, pp. 110B117.  "

OR-4. Iodine-131 in the Treatment of Malignant Melanoma

THERAPEUTIC TRIALS were conducted at the Oak Ridge Institute of Nuclear Studies in 1951 to investigate the use of iodine­131 (I¹³¹) in the treatment of malignant melanoma. A secondary objective was to determine the distribution of I¹³¹ in patients with this type of tumor both in the presence and in the absence of functioning thyroid tissue.

Two subjects were studied. The first subject was a 37­year­old man in the terminal stages of metastatic malignant melanoma of the liver. He received 100 microcuries of I¹³¹ orally. Three days later, the subject was given 57.6 millicuries of I¹³¹ orally. Tissue samples were obtained during the autopsy, 6 days after ingestion of the I¹³¹.

The second subject was a 43­year­old woman with malignant melanoma of the arms and legs. This patient received three oral doses of I¹³¹ (305 millicuries, 69.7 millicuries, and 69.7 millicuries). Tissues samples were obtained by biopsy after each dose. Iodine-131 failed to localize the tumor and was judged ineffective for therapy of melanoma by this method. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Andrews, G.A., and M. Brucer. ARadioactive Iodine in Malignant Melanoma.@Medical Division Quarterly Report October 1BDecember 31, 1953. Oak Ridge, TN: Oak Ridge Institute of Nuclear Studies, pp. 12B16. Oak Ridge Institute of Nuclear Studies, ORAU Medical Science Division, Vance Road Facility, Room 202A, ORAU­30022.   "

OR-5. Use of Iodine-131 Following Surgical Removal of Thyroid Cancers

BETWEEN 1950 AND 1974, 117 patients admitted to the Oak Ridge Institute of Nuclear Studies, Oak Ridge Associated Universities, with cancer of the thyroid, received at least one dose of therapeutic administration of iodine­131 (I¹³¹) as a followup to surgical removal of the tumors. The purpose of the I¹³¹ was to destroy any possible cancerous thyroid tissue that was not removed surgically.

The project was terminated in October 1974 and ORAU personnel began compiling data and evaluating the clinical course of the patients. Eighty­seven of these patients were still alive at that time. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

AUse of Radioiodine in Surgical Removal of Thyroid Cancers.@Oak Ridge Associated Universities, Medical Division, Committee on Human Studies File (Project No. 5). Oak Ridge, TN: Oak Ridge Institute for Science and Education. Medical Sciences Division, 1973, ORAU/ORNL Committee. Vance Road Facility, Room 202A, ORAU­30016, File 1.  "

OR-6. Comparison of the Metabolism of Rubidium-86 and Potassium-42

IN 1953, four patients at Oak Ridge Institute for Nuclear Studies with leukemia and carcinoma, participated in tracer studies to determine whether rubidium­86 (Rb⁸⁶) could be used as an analog for potassium­42 (K⁴²) in studying biological systems. Simultaneous intravenous injections of K⁴² and Rb⁸⁶ were administered to the study participants. Multiple samples of plasma, red cells, and urine were obtained and analyzed from each patient.

The researchers concluded that Rb⁸⁶ was a satisfactory substitute for K⁴² in biological studies. This work was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

APotassium­42 and Rubidium­86 Studies.@Medical Division Quarterly Report October 1BDecember 31, 1953. Oak Ridge, TN: Oak Ridge Institute of Nuclear Studies, pp. 10B11. Oak Ridge Institute of Nuclear Studies, ORAU Medical Science Division, Vance Road Facility, Room 202A, ORAU­30022.

Tyor, M.P., and J.S. Eldridge. AA Comparison of the Metabolism of Rb⁸⁶ and K⁴² Following Simultaneous Injection into Man.@Presented to American Society for Clinical Investigation, Atlantic City, April 1954.  "

OR-7. Metabolism Studies Using Calcium­47

IN 1959, the metabolism of calcium was studied at the Oak Ridge Institute of Nuclear Studies. Eleven patients with various diseases, including bone lesions and breast cancer, were given calcium­47 (Ca⁴⁷).

Two of the patients were administered 70 microcuries intravenously and two patients received oral dosages of 138 and 104 microcuries, respectively. One patient received both an intravenous and an oral dose. Analyses for Ca⁴⁷ were then made on blood, urine, feces, and saliva. Whole-body retention of Ca⁴⁷ was also determined. Comparisons were made between intravenous and oral routes of administration. This research was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

ACalcium-47 Studies in Patients.@Medical Division Report for 1959. Oak Ridge: Oak Ridge Institute of Nuclear Studies, p. 33. Oak Ridge Institute of Nuclear Studies, Oak Ridge Associated Universities Medical Sciences Division, Vance Road Facility, Room 202-A, ORAU-3 C54, File 2.

Monthly Highlight Report. Oak Ridge Institute of Nuclear Studies, Medical Division, June 1960. NARA Atlanta Archives, RG 326­68A1096, OR Research Division, Organization and Management­5, Box 400, Folder AOrganization and Management­8, ReportCORINS.@ "

OR-8. Total-Body Irradiation Therapy of Hematologic Disorders

BETWEEN 1956 TO 1973, the Oak Ridge Institute for Nuclear Studies, Oak Ridge Associated Universities Medical Division studied the efficacy of total-body irradiation (TBI) on the treatment of hematological disorders, particularly leukemia, polycythemia rubra vera, and lymphoma. The purposes were to develop improved methods for irradiation therapy, to develop improved methods for assessing and treating accidental gamma and neutron radiation, to compile and evaluate related data, and to identify new and more precise endpoints that define human radiation dose­response.

The 194 male and female patients, all diagnosed with hematologic malignancy, ranged in age from 12 to 86 years. They were exposed to totals of 50 to 300 roentgens per treatment series. However, in 1970, one patient was exposed to 500 roentgens in preparation for an attempted bone marrow graft. The external gamma radiation sources were either cobalt­60 (Co⁶⁰) or cesium­137 (C¹³⁷) used in two types of facilities: a medium-exposure­rate total-body irradiator (METBI) providing an exposure rate of 1.5 roentgens per minute from C¹³⁷ and sources, and a low­exposure­rate total-body irradiator (LETBI) providing an exposure rate of 1.5 roentgens per hour from Co⁶⁰ sources.

There was a higher frequency of remissions after 150 roentgens compared to 250 roentgens. The results showed that TBI-treated patients survived about as long as, but not significantly longer than, patients treated by standard chemotherapy. The use of TBI in conjunction with splenectomy in the treatment of one patient with chronic granulocytic leukemia was studied, but the response to the combined therapy was similar to TBI alone. The program, which was discontinued in 1974, was funded by the U.S. Atomic Energy Commission. (TBI was referenced in the Markey report and included in The DOE Roadmap of February 1995, and since revised.)

References

Andrews, G.A., R.M. Kniseley, H. Vodopick, P.E. Bergner, and C.C. Lushbaugh. AHematologic Responses to Total­Body Irradiation.@In Radioisotope in Pharmakokinetick und Klinischer Biochemie, edited by G. Hoffman and H.A. Ladner, pp. 517B527. Stuttgart: Nuklear Medizin, 1966.

Andrews, G.A., F.V. Comas, C.L. Edwards, R.M. Kniseley, C.C. Lushbaugh, and H. Vodopick. AHematologic and Therapeutic Effect of TBI in Patients with Malignant Lymphoma, Chronic Lymphocytic, and Granulocyte Leukemias, and Polycythemia Vera.@Washington, D.C.: U.S. Atomic Energy Commission, ORAU­112, 1970.

Andrews, G.A., C.C. Lushbaugh, R.M. Kniseley, D. White, and B.I. Friedman. AHematological Effects of Whole-Body Irradiation in the Human Being.@In IAEA Panel: Effects of Ionizing Radiation on the Hematopoietic Tissue. Vienna: International Atomic Energy Agency, 1970, pp. 75B83.

Edwards, C.L., C.C. Lushbaugh, H. Vodopick, F.A. Goswitz, B. Nelson, R.M. Kniseley, and G.A. Andrews. AStudies of Total­Body Irradiation in Patients with Hematological Disorders.@Application for Use of Humans As Experimental Subjects. Oak Ridge: TN, Oak Ridge Associated Universities Medical Division, Committee on Human Studies and Related Documentation (Project No. 10), 1969. Oak Ridge Institute for Science and Education. Medical Sciences Division. ORAU/ORNL Committee. Vance Road Facility, Room 202A, ORAU­30016, File 1.

AClinical Observations: Therapeutic Total-Body Irradiation.@1972 Research Report. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, ORAU­122, pp. 6B14.

ARadiation Effects and Related Topics: Clinical Total-Body Irradiation.@1970 Research Report. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, ORAU­113, p. 4.

ARadiation Effects and Related Topics.@1973 Research Report. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, ORAU­123, pp. 4B12.

Hearings before the Subcommittee on Investigations and Oversight, September 23, 1981. Human Total Body Irradiation Program at Oak Ridge. Washington, D.C. (the Gore Hearings)

Monthly Highlight Report for January 1960. Oak Ridge, TN:Oak Ridge Institute of Nuclear Studies, Medical Division, February 3, 1960, p. 2.  "

OR-9. Studies Using Cobalt-57BLabeled Vitamin B₁₂

THIS RESEARCH, conducted in the early 1960s, was a collaborative effort between the Oak Ridge Institute of Nuclear Studies; the Long Island Jewish Hospital, Jamaica, New York; South Nassau Communities Hospital, Oceanside, New York; and Brookhaven National Laboratory. The studies sought to determine why the serum and plasma levels of vitamin B₁₂ were elevated in patients with chronic myelocytic leukemia.

In one study, three patients in remission were intravenously administered 0.13 microcurie of vitamin B₁₂ labeled with Co⁵⁷. The procedure was repeated twice in the same patients, after administration of loading doses of vitamin B₁₂.

In another study, 10 patients with various degrees of chronic myelocytic leukemia and 5 healthy individuals each received 3 or more intravenous injections of Co⁵⁷-labeled B₁₂. This research was supported by a grant from the National Cancer Institute and by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Meyer L.M., L.M. Schiffer, D.A. White, and E.P. Cronkite. AThe Plasma Disappearance of Radioactive Cyanocobalamin: Effect of Prior Administration of Vitamin B₁₂ Analogues.@British Journal of Hematology. Vol. 11, No. 3, May 1965, pp. 370B379.

Monthly Highlight Report. Oak Ridge, TN: Oak Ridge Institute of Nuclear Studies, Medical Division, December 1962. NARA Atlanta Archives, RG 326­68A1096, OR Research Division, Organization and Management 5, Box 400, Folder AOrganization and Management­8, Reports CORINS.@ "

OR-10. Iodine-131BLabeled L-Thyroxine Turnover by Whole-Body Counting

DURING 1966 AND 1967, a study was conducted by the Oak Ridge Institute of Nuclear Studies, Oak Ridge Associated Universities to compare the turnover of L­thyroxine (thyroxine is an iodine-containing hormone that exists normally in the thyroid gland) in subjects with hyperthyroidism, hypothyroidism, and normal thyroid functions.

Twenty to 40 microcuries of iodine-131 (I¹³¹) labeled L-thyroxine were administered by intravenous injection to each of 10 patients with abnormal L­thyroxine metabolism and to 5 normal, healthy subjects for comparison. Body counting was conducted twice on the first day after the I¹³¹­labeled L­thyroxine was administered, and daily thereafter. Daily thyroid counts were made on the subjects by standard methods. In addition, blood samples were obtained from five patients to compare blood turnover rates to whole-body counts with those of the patients with thyroid disease.

This study showed that whole-body counting provided quantitative information on the turnover of L­thyroxine. This work was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Bird, E.D., and W.D. Gibbs. AL­thyroxine Turnover by Whole-Body Counting in Patients Receiving Exogenous Thyroid Hormone.@1968 Research Report. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Sciences Division, 1968, pp. 223B227. Oak Ridge Institute for Science and Education, ORAU Medical Sciences Division, ORAU­30002, Part 3 of 6.  "

OR-11. Experimental Tumor Scanning with Gallium-67

FROM 1969 THROUGH 1977, Oak Ridge Associated Universities conducted studies on the use of gallium­67 (Ga⁶⁷) as a tumor­scanning agent in humans. Participating were 357 male and female patients ranging in age from 6 to 83 years. All had known, viable bone or soft tissue tumors associated with a wide variety of cancers.

All patients received at least one intravenous injection of 70 microcuries of Ga⁶⁷ per kilogram of body weight, up to a total amount of 6 millicuries. Thirty­four of these patients received more than one injection. Several received a series of injections to study the therapeutic effect and to look for recurrence of disease.

In a related study, four patients were administered Ga⁶⁷ by injection into the lymphatic structure of the feet.

These studies showed that gallium did not collect equally in all types of tumors. Rather, it collected in tumors of specific cellular types. The lymphatic injections showed no advantage to this approach, even in identifying tumors along the lymphatic vessels. In May 1976, the U.S. Food and Drug Administration approved Ga⁶⁷ citrate for general diagnostic use. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Edwards, C.L., R.L. Hayes, N. Tehranian, R. Kniseley, F. Goswitz, R. Tanida, and H. Vodopick. ATumor Scanning with Gallium­67.@Application for Use of Humans As Experimental Subjects, Medical Division, Oak Ridge Associated Universities, Committee on Human Studies and Related Documentation (Project No. 9). Oak Ridge, TN: Oak Ridge Institute for Science and Education, Medical Sciences Division. 1969 ORAU/ORNL Committee. Vance Road Facility, Room 202A, ORAU­30016, File 1.

Nelson, B., R.L. Hayes, C.L. Edwards, R.M. Kniseley, and G.A. Andrews. ADistribution of Gallium in Human Tissues After Intravenous Administration.@Journal of Nuclear Medicine. Vol. 13, 1972, pp. 92B100.

ATumor Scanning with Gallium­67.@1970 Research Report. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Sciences Division, 1970, pp. 100B105. Oak Ridge, TN: Oak Ridge Institute for Science and Education, ORAU Medical Sciences Division, ORAU­30002, Part 3 of 6.  "

OR-12. Therapeutic Allogenic Transplant-ation of Human Bone Marrow

FROM 1970 TO 1973, Oak Ridge Associated Universities conducted a study to evaluate the effectiveness of combining high­dose total-body irradiation (TBI) with antilymphocyte­globulin as an immunosuppressive regimen to induce tolerance to a foreign bone marrow graft in humans.

Three patients were involved initially. Each was exposed to 500 roentgens, which corresponded to an average total-body absorbed dose of approximately 370 rads. Subsequent bone marrow grafts were successful in two patients. Failure of the graft in the third patient was determined to have resulted from an insufficient radiation dose. Accordingly, researchers requested and received approval to increase the exposure level to deliver an absorbed dose of 800 rads at the rate of 40 roentgens per minute.

The original protocol limited patients to those with acute leukemia. Researchers also requested and received approval to extend the procedure to patients with aplastic anemia. A fourth patient, with acute leukemia, was treated in 1973. This patient was exposed to a 694 roentgens total-body irradiation (TBI), but developed a severe graft­versus­host reaction that prevented a successful marrow transplant.

The Oak Ridge Institute of Nuclear Studies conducted a related study beginning in 1971 that was designed to identify objective signs and distinguish early graft­versus­host reactions from drug reactions, infections, and other complications related to or incidental to the marrow transplant/TBI procedure. In this study, skin biopsies were obtained from four patients or volunteers, without further exposing them to radiation of any kind.

This work was supported by the U.S. Atomic Energy Commission. (TBI was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Andrews, G.A. AThe Therapeutic Use of Bone­Marrow Transplantation.@In Proceedings of the International Conference on Leukemia­Lymphoma, edited by C.J.D. Zarafonetis, pp. 423B432. Philadelphia: Lea and Febiger, 1968.

Gengozian, N., C.L. Edwards, H. Vodopick, and K. Hubner. ATherapeutic Allogenic Transplantation of Human Bone Marrow.@Application for Use of Humans As Experimental Subjects. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, Committee on Human Studies and Related Documentation (Project No. 13), 1970. Oak Ridge Institute for Science and Education. Medical Sciences Division. ORAU/ORNL Committee. Vance Road Facility, Room 202A, ORAU­30016, File 1.

Nelson, B., and L. Edwards. AHistologic Changes in the Skin Related to the Graft vs Host (GVH) Reaction After Marrow Transplantation.@Application for Use of Humans As Experimental Subjects. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, Committee on Human Studies and Related Documentation (Project No. 15),1970. Oak Ridge Institute for Science and Education. Medical Sciences Division. ORAU/ORNL Committee. Vance Road Facility, Room 202A, ORAU­30016, File 1.

AAllogenic Marrow Transplantation in Man.@1971 Research Report. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, 1971, ORAU­116, pp. 65B70.

ATherapeutic Allogenic Bone­Marrow Transplantation.@1973 Research Report. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, 1973, ORAU­123, pp. 39B43.  "

OR-13. Scandium­Augmented Gallium-67 Localization in Tumors

FROM 1972 TO 1973, Oak Ridge Associated Universities conducted a study to determine whether intravenous administration of stable scandium citrate along with radioactive gallium increased the relative concentration of the gallium in tumors.

The study protocol proposed administration of scandium in doses ranging from 0.005 to 1.0 milligram per kilogram of body weight, followed by 100 microcuries of gallium­67 to 21 patients with known malignancies. The first patient to be treated experienced an adverse reaction to the scandium citrate but made a satisfactory recovery. Testing was suspended pending further investigation. There is no indication of further study. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Hayes, R.L., C.L. Edwards, and B.M. Nelson. AScandium­Augmented Gallium Localization in TumorsCPhase I and Phase II Studies.@Application for Use of Humans As Experimental Subjects. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, Committee on Human Studies and Related Documentation (Project No. 18), 1971. Oak Ridge Institute for Science and Education. Medical Sciences Division. ORAU/ORNL Committee. Vance Road Facility, Room 202A, ORAU­30016, File 1.

Hayes, R.L., and C.L. Edwards. AThe Effect of Stable Scandium on Red Blood Cells and the Retention and Excretion of Ga⁶⁷ in Humans.@Southern Medical Journal. Vol. 66, 1973, pp. 1,339B1,340.  "

OR-14. Clinical Testing of Strontium-85m as a Bone Scanning Agent

FROM 1972 TO 1975, Oak Ridge Associated Universities conducted a study of strontium­85m (Sr^85m) as a bone scanning agent. Patients with known malignant tumors or suspected metastatic disease of the bone were administered up to 30 microcuries of Sr^85m per kilogram of body weight (approximately 2 microcuries per patient) by intravenous infusion. Results of the Sr^85m scans were compared with subsequent scans using strontium­85, fluorine­18, or technetium­99m. Four patients were involved in the study. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

AClinical Testing of Strontium­85m as a Bone Scanning Agent.@Application for the Use of Humans as Experimental Subjects. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, Committee on Human Studies and Related Documentation (Project No. 25), 1972. Oak Ridge Institute for Science and Education, Medical Sciences Division, ORAU/ORNL Committee, Vance Road Facility, Room 202A, ORAU­30016, File 1.  "

OR-15. Comparison of Indium-111 and Bismuth-206 with Gallium-67 as Tumor Scanning Agents

FROM 1972 TO 1978, Oak Ridge Associated Universities conducted a study to determine the relative merits of indium­111 (In¹¹¹) and bismuth­206 (Bi²⁰⁶) when compared to gallium­67 (Ga⁶⁷) as tumor imaging agents. In actual application, the study was limited to evaluating In¹¹¹ and Ga⁶⁷.

In 1973, six cancer patients received simultaneous injections of In¹¹¹ (0.011 microcurie per kilogram of body weight) and Ga⁶⁷ (0.045 microcurie per kilogram). Three additional patients were studied during 1974.

The study showed that Ga⁶⁷ was a better tumor scanning agent than In¹¹¹. After July 1974, no patients were scanned with In¹¹¹ at Oak Ridge. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

AComparison of Indium­111 and Bismuth­206 with Gallium­67 as Tumor Scanning Agents.@Application for Use of Humans As Experimental Subjects. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, Committee on Human Studies and Related Documentation (Project No. 22), 1972. Oak Ridge Institute for Science and Education. Medical Sciences Division. ORAU/ORNL Committee. Vance Road Facility, Room 202A, ORAU­30016, File 1.

AIndium­111 and Ga⁶⁷ for Tumor Scanning.@1973 Research Report. Oak Ridge, TN: Medical Division, Oak Ridge Associated Universities, ORAU­123, 1973, pp. 77B82.  "

OR-16. Use of an External Gadolinium-153 Source for Timing the Cardiac Cycle

FROM 1972 TO 1975, Oak Ridge Associated Universities conducted a study to determine the effectiveness of gadolinium­153 (Gd¹⁵³) as a noninvasive technique for evaluating specific stages of the cardiac cycle, notably the left ventricular ejection time.

A fine beam of gamma radiation from a Gd¹⁵³ source, which was placed on the subject=s back, was directed through the heart to a detector on the subject=s chest. At least six patients were subjected to a radiation exposure of approximately 0.2 roentgen over a 1­inch­diameter area on their backs. The passage of blood through the left ventricle was determined by measuring the blockage of gamma rays emitted by the Gd¹⁵³. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Oder, C., A.C. Morris, L. Edwards, and J. Berger. AUse of External Gadolinium­153 Source for Timing of Parts of Cardiac Cycle.@Application for the Use of Humans as Experimental Subjects. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, Committee on Human Studies and Related Documentation (Project No. 23), 1972. Oak Ridge Institute for Science and Education, Medical Sciences Division, ORAU/ORNL Committee, Vance Road Facility, Room 202A, ORAU­30016, File 1.  "

OR-17. Dysprosium-157 as a Clinical Imaging Agent for Solid Tumors

FROM 1973 TO 1977, Oak Ridge Associated Universities conducted a study to determine whether dysprosium­157 (Dy¹⁵⁷) could be used effectively as a tumor localizing agent in humans. Both bone tumors and soft­tissue tumors were considered. Thirty­four patients with known cancer were included.

This study was discontinued in 1977 after the investigators found that Dy¹⁵⁷ did not provide better images of solid tumors than the technetium­99m phosphate compounds did for bone scans, nor was it better than gallium­67 citrate for soft-tissue tumors. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Edwards, C.L., R.L. Hayes, and J.K. Poggenburg. ADysprosium­157 as a Clinical Scanning Agent for the Detection of Osseous and Nonosseous Tumors.@Application for the Use of Humans as Experimental Subjects. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, Committee on Human Studies and Related Documentation (Project No. 35), 1973. Oak Ridge Institute for Science and Education, Medical Sciences Division, ORAU/ORNL Committee on Human Studies, Vance Road Facility, Room 202, ORAU­30017, File 2.  "

OR-18.

(Included in The DOE Roadmap and now part of OR-8)

OR-19. Clinical Testing of a Line-Scanning Proportional Counter Camera Using Injected Iodine-125 and Technetium-99m

DIAGNOSTIC DOSES OF IODINE-125 and technetium­99m were administered to selected patients referred to Oak Ridge Associated Universities from the Oak Ridge Methodist Hospital for thyroid evaluation. The quality of images obtained by the camera using the two radioisotopes was evaluated and compared. Although these subjects were evaluated for preexisting disease, certain aspects of this study were experimental, and the objective was development of instrumentation and techniques for evaluating human thyroids. An estimated 100 subjects were studied. This study was conducted between August 27, 1975, and September 29, 1977. (Previously described in #33 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Andrews, G.A., W. Gibbs, C. Borkowski, K. Hubner, and J. Harter. AClinical Testing of a Line Scanning Proportional Counter Camera.@Application for Use of Humans As Experimental Subjects. Oak Ridge, TN: Oak Ridge Associated Universities, Medical Division, Committee on Human Studies and Related Documentation (Project No. 41), 1975. Oak Ridge Institute for Science and Education. Medical Sciences Division. ORAU/ORNL Committee on Human Studies, Vance Road Facility, Room 202A, ORAU­30017, File 2.

Brill, A.B. ARadioisotope Studies Utilizing a Low Level Whole-Body Counter and Clinical Applications of Activation Analysis.@ERDA Progress Report. Nashville, TN: Vanderbilt University, April 30, 1975, p. 75. Oak Ridge Operations Office, Records Holding Area, Documents 1944B1994, Box H­101­12, Bldg. 2714­H, Folder 2401, AReports May/July 1976, Vanderbilt University.@

Brill, A.B. ARadioisotope Studies Utilizing a Low Level Whole-Body Counter and Clinical Applications of Activation Analysis.@ERDA Progress Report. Nashville, TN: Vanderbilt University, July 31, 1977. Oak Ridge Operations Office, Records Holding Area, Documents 1944B1994, Box H­101­12, Bldg. 2714­H.  "

OR-20. Uranium Injections Into Terminally Ill Cancer Patients

FROM 1953 TO 1957, Oak Ridge National Laboratory and Massachusetts General Hospital conducted a cooperative study on the distribution and excretion of uranium in humans using terminally ill brain cancer patients as subjects. Participants included male and female patients ranging in age from 26 to 63 years. All were near death (in a coma or semicoma) prior to injection and were receiving usual hospital care for comatose patients.

Subjects were intravenously administered uranium­233 or uranium­235 as either uranyl nitrate hexahydrate (nine patients) or uranium tetrachloride (two patients) in amounts ranging from 4 to 50 milligrams.

The subjects died from their brain cancer within several months of injection. Study results indicated that 99 percent of the injected uranium cleared the blood within 20 hours, either depositing in the skeleton and kidneys or exiting through urine. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Bernard, S.R. AMaximum Permissible Amounts of Natural Uranium in the Body, Air, and Drinking Water Based on Human Experimental Data.@Health Physics. Vol. 1, 1958, pp. 288B305.

Bernard, S.R., J.R. Muir, and G.W. Royster, Jr. AThe Distribution and Excretion of Uranium in Man.@In Proceedings of the Health Physics Society. June 1956, pp. 33B48.

Luessenhop, A.J., J.C. Gallimore, W.H. Sweet, E.G. Struxness, and J. Robinson. AThe Toxicity in Man of Hexavalent Uranium Following Intravenous Administration.@American Journal of Roentgenology, Radium Therapy and Nuclear Medicine. Vol. 79, No. 1, 1958, pp. 83B100.

Struxness, E.G., A.J. Luessenhop, S.R. Bernard, and J.C. Gallimore. AThe Distribution and Excretion of Hexavalent Uranium in Man.@In Proceedings of the International Conference on the Peaceful Uses of Atomic Energy, pp. 186B196. New York: United Nations, 1956.  "

 ‡  ‡  ‡

OR-21. Pathologic Changes in Normal Thyroid Tissue After Large Doses of Iodine-131

IN THE EARLY 1950s, physicians at the Oak Ridge Institute of Nuclear Studies studied the histopathology of normal thyroid tissue subjected to high-dose radiation from incorporated iodine-131 (I¹³¹). Ten hospital patients were included in this study (four men and six women). All required the removal of their thyroids for treatment of thyroid cancer, except for one patient with advanced metastatic melanoma (a tumor of melanin-pigmented cells in skin and elsewhere) who had a poor prognosis and short life expectancy. The purpose of this study was to evaluate the effectiveness of I¹³¹ in destroying normal thyroid tissue, which was considered to be a relatively radioresistant tissue.

Three of the patients received large amounts of I¹³¹ (totaling between 81 and 298 microcuries, which were intended to destroy the thyroid by radiation alone. Six received smaller but varying amounts totaling between 28 and 75 microcuries followed by thyroidectoy (surgical removal of the thyroid gland) 2 and 13 days after administration. The one remaining subject received a diagnostic rather than destructive amount totaling 75.4 microcuries but did not undergo surgery until 42 days after the initial administration of I¹³¹. Thyroid tissues were histologically studied to determine the pathological effects of radiation and degree of completeness as a function of the radiation absorbed dose.

For 9 of the 10 subjects, the administration of radioiodine constituted beneficial medical therapy. The study of the effects of I¹³¹ on the thyroid of the terminal melanoma patient was not related to therapy. This study provided new information on the response of thyroid tissue to relatively large dosages from I¹³¹. Variations in response were observed among the patients treated, and response was not well correlated with radiation absorbed dose. Complete necrosis of normal thyroid tissue was not observed, even following administration of large amounts of I¹³¹. This experiment was supported by the U.S. Atomic Energy Commission.

References

Andrews, G., R. Kniseley, R. Bigelow, S. Root, and M. Brucer. APathologic Changes in Normal Human Thyroid Tissue Following Large Doses of I¹³¹.@American Journal of Medicine. Vol. 16, March 1954, pp. 372B381.  "

OR-22. Intracavitary Injection of Phosphate-32 as Colloidal Chromic Phosphate

IN THE EARLY 1950s, researchers in the Medical Division of the Oak Ridge Institute of Nuclear Studies conducted a study examining the metabolism and distribution of chromic phosphate (CrPO₄) labeled with phosphorus-32 (P³²) after intracavitary administration. Four patients with pleural effusion (fluid accumulation in the lungs) and six with ascites (fluid accumulation in the abdominal cavity associated with cancer) were chosen as subjects.

Subjects received an intracavitary injection of between 2.2 and 19.5 millicuries of colloidal P³² chromic phosphate. Following the intraperitoneal administration, the levels of P³² activity in the blood, urine, and the pleural and peritoneal fluids were measured at various time intervals. Tissue distribution of P³²-chromic phosphate also was studied in tissues obtained at autopsy from three patients who died as a consequence of their disease during the period of observation. The researchers concluded that colloidal P³²-chromic phosphate had potential to be useful in intracavitary therapy. This research was funded by the U.S. Atomic Energy Commission.

References

Root, S., M. Tyor, G. Andrews, and R. Kniseley. ADistribution of Colloidal Radioactive Chromic Phosphate After Intracavitary Administration.@Radiology. Vol. 63, August 1954, pp. 251B259.  "

OR-23. Experimental Treatment of Chronic Leukemia Using Colloidal Gold-198

IN THE EARLY 1950s, physicians in the Medical Division of the Oak Ridge Institute of Nuclear Studies used colloidal gold-198 (Au¹⁹⁸) in the treatment of chronic leukemia. Six patients with previously untreated chronic leukemia and two additional patients with late-stage treated leukemia, were included in the study and followed for 3 to 8 months.

All patients in this study received from 23.0 to 45.5 millicuries of Au¹⁹⁸ by intravenous injection. Three patients with previously untreated disease also received a second administration 2.5 to 5 months after the initial injection. Levels of Au¹⁹⁸ activity were measured in the plasma, urine, and the red and white blood cells of the patients.

External counting studies using collimated gamma detectors showed that Au¹⁹⁸ concentrated in the liver and spleen. All the patients with untreated leukemia exhibited a reduction in the size of the liver and spleen; five of the six showed an improvement in red cell values. Little or no improvement was observed in two patients with late stage disease. This research was supported by the U.S. Atomic Energy Commission.

References

Andrews, G.A., and M.P. Tyor. AEarly Results of the Treatment of Chronic Granulocytic Leukemia with Intravenous Colloidal Gold-195.@Journal of Laboratory and Clinical Research. Vol. 42, No. 5, 1953, pp. 777B778.  "

OR-24. Intracavitary Colloidal Gold-198 in the Treatment of Effusions Due to Malignant Neoplasms

BETWEEN 1950 AND 1952, researchers in the Medical Division of the Oak Ridge Institute of Nuclear Studies conducted a pioneering program in the intracavitary use of colloidal gold (Au¹⁹⁸) for treatment of effusions (fluid accumulations) caused by malignant tumors. This treatment was expected to be palliative (resulting in relief, not cure); however, its ultimate value was unknown. The treatment program also provided the opportunity to study the metabolism, distribution, and tissue effects of Au¹⁹⁸ in humans.

Over the 2-year period, 39 patients with tumor-related accumulations of fluid in one or more body cavities received intracavitary Au¹⁹⁸ treatment to eliminate or reduce the fluid accumulations. This was done as an alternative to the conventional regimen of drainage of the fluid followed by x­ray therapy. The patients included both men and women ranging in age from 18 to 76 years.

The amount of radioactivity given was patient-specific, with typically 75 and 150 millicuries of colloidal Au¹⁹⁸ being injected directly into the abdominal and pleural cavities, respectively. Some patients required multiple treatments over several weeks. The largest amount of Au¹⁹⁸ given in a single administration was 187 millicuries. The largest total amount administered to a single patient was 659 millicuries over a 10-month period. In anticipation of postmortem studies, small additional amounts of Au¹⁹⁸ were given to patients whose death appeared imminent if the previously administered Au¹⁹⁸ had largely decayed. Daily blood and urine samples were measured for radioactivity. Activity retained in the body was assessed by Geiger counters. Tissue samples were obtained during routine surgical procedures or at autopsy.

Patients typically experienced some gastrointestinal effects of varying severity beginning 12 to 24 hours after Au¹⁹⁸ administration and lasting for 2 to 3 days. However, there were no serious or prolonged adverse reactions, even with the largest amounts of Au¹⁹⁸. Slight, transient bone marrow depression was observed in most patients. Twenty-three patients experienced some degree of relief from fluid accumulations; no effect was observed in 2; evaluation was not possible in 14 patients because of early death from the underlying tumor or because of combined therapy.

Tissue studies showed that Au¹⁹⁸ tends to be absorbed at the cavity surfaces rather than entering the tumor tissue. There was little evidence of radiation-induced changes in the tumors. A small amount of Au¹⁹⁸ was found to have migrated slowly into the lymphatic system, and measurable amounts were detectable in major organs. A small amount of Au¹⁹⁸ was excreted in the urine. Evidence of benefit of Au¹⁹⁸ treatment in these cases appeared to be confined to the control of fluid accumulation, but the frequency and severity of adverse effects were less than with conventional therapy. This research was supported by the U.S. Atomic Energy Commission.

References

Andrews, G.A., S.W. Root, H.D. Kerman, and R.R. Bigelow. AIntracavitary Colloidal Radiogold in the Treatment of Effusion Caused by Malignant Neoplasms.@Annals of Surgery. Vol. 137, 1953, pp. 375B382.

Andrews, G.A., S.W. Root, and R.M. Kniseley. AMetabolism and Distribution of Colloidal Gold injected into Serous Cavities for Treatment of Effusion Associated with Malignant Neoplasm.@Cancer. Vol. 6, 1953, pp. 294B302.

Andrews, G.A., S.W. Root, R.M. Kniseley, and H.D. Kerman. AIntracavitary Use of Colloidal Radioactive Gold.@Radiology. Vol. 61, 1953, pp. 922B929.

Kniseley, R., and G.A. Andrews. APathological Changes Following Intracavitary Therapy with Colloidal Au¹⁹⁸.@Cancer. Vol. 6, 1953, pp. 303B312.

Stembridge, V.A., R.M. Kniseley, and G.A. Andrews. ACellular Changes in Effusions Following Intracavitary Administration of Colloidal Au¹⁹⁸ in Human Beings.@Journal of Laboratory and Clinical Medicine. Vol. 41, 1953, pp. 760B766.  "

OR-25. Study of Strontium and Calcium Metabolism Using Strontium-85 and Calcium-45

BETWEEN 1955 AND 1957, researchers at the Oak Ridge Institute of Nuclear Studies conducted a series of experiments to learn more about the comparative metabolisms of strontium and calcium. The purpose of this research was to better understand the competition between strontium and calcium and the various processes that determine their uptake, retention, and excretion. A further purpose was to study strontium metabolism after single and continuous intakes.

The study subjects were 13 chronically ill patients C6 men and 7 womenCwith leukemia or other widespread malignant diseases of various types. The patients ranged in age from 9 to 73 years. Seven patients were administered one oral or intravenous dosage of between 5 and 20 microcuries of strontium-85 (Sr⁸⁵) while consuming an exclusively nonmilk diet. Four of these seven later received an equal amount of Sr⁸⁵ while consuming a normal milk intake. Two patients ingested 1 to 3 microcuries of Sr⁸⁵ per meal for about 20 days. Four other subjects received 1 to 3 microcuries of Sr⁸⁵ and 2 to 6 microcuries of calcium-45 (Ca⁴⁵) per meal for 5 to 20 days.

Urine and fecal samples were collected from each patient for Sr⁸⁵ and Ca⁴⁵ analysis. Blood samples were also obtained from some of the patients to determine levels of Sr⁸⁵ in plasma over time. Tissue samples were obtained from some of the patients at autopsy.

This study showed that Sr⁸⁵ concentrations measured early in the experiment in blood, kidneys, spleen, thyroid, bones, and bone marrow were all approximately the same. These concentrations were much higher, however, than those measured in other tissues. When measured later, the strontium concentrations were higher in bones and lower in blood and soft tissues than those absorbed earlier. Calcium was absorbed more readily, and excreted less readily, than strontium. This research was supported by the U.S. Atomic Energy Commission.

References

Comar, C., R. Wasserman, W. Ullberg, and G. Andrews. AStrontium Metabolism and Strontium-Calcium Discrimination in Man.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 95, 1957, pp. 386B391.  "

OR-26. Gastrointestinal Tract Studies Using Lanthanum-140 and Iron-59

IN THE EARLY 1960s, researchers in the Medical Division of the Oak Ridge Institute of Nuclear Studies used lanthanum-140 (La¹⁴⁰) citrate in human studies. The purpose was to investigate the importance of individual variations that may result in radiation dose to the intestinal tract from internal emitters.

In the first study, the subjects were 54 patients having normal intestinal tracts who were administered 10 to 20 microcuries of La¹⁴⁰ in the citrate form under a variety of meal scenarios (2 hours before breakfast, with the noon meal, etc.) The purpose was to verify the assumptions being used at that time to describe a standardized intestinal tract in man. The results of this study showed that radiation dose estimates for individuals could vary significantly from dose estimates derived from generalized models.

In the second study, La¹⁴⁰ was used to verify the completeness of information from analysis of stool collections for gastrointestinal absorption tests and to calculate the loss of unabsorbed iron-59 (Fe⁵⁹) when fecal collections are incomplete. Twenty-one patients participated as subjects in this study, with one subject receiving two treatments. Subjects received 20 microcuries of La¹⁴⁰ and 2 microcuries of Fe⁵⁹ orally. Results of the study indicated that La¹⁴⁰ could be used to determine incomplete collections of stool samples, but that it could not be used to calculate the loss of unabsorbed Fe⁵⁹ because the rates of passage through the intestinal tract are different. This study was supported by the U.S. Atomic Energy Commission.

References

Hayes, R.L., J.E. Carleton, and W.R. Butler. ARadiation Dose to the Human Intestinal Tract from Internal Emitters.@Health Physics: Official Journal of the Health Physics Society. Vol. 9, 1963, pp. 915B920.

Hayes, R.L., J.E. Carleton, and W.R. Butler. ALanthanun-140 as a Measure of the Completeness of Stool CollectionsCDemonstration of Delayed Excretion of Iron-59.@Journal of Nuclear Medicine. Vol. 5, 1964, pp. 200B208.  "

OR-27. Total-Body Irradiation and Attempted Bone Marrow Transplants in Acute Leukemia

IN A STUDY REPORTED IN 1961, researchers in the Medical Division of the Oak Ridge Institute of Nuclear Studies investigated combined total-body irradiation and bone marrow transplants as a possible treatment of leukemia. The researchers recognized that hazards were associated with the treatment of patients who had a very poor prognosis, had already been treated by means of chemotherapy, and were in clinical and hematologic relapse.

Eleven subjectsCnine males and two femalesCwere included in the study. Seven of the 11 subjects were children with acute leukemia of the primitive cell type. Nine of the subjects received various doses of radiation from cobalt-60 (Co⁶⁰) ranging from 210 to 940 rads in single administrations. One of the subjects received a total of 1,000 rads in two fractions (380 and 620 rads) 5 months apart. Another subject received 940 rads over a 9-day period. Seven of the subjects received bone marrow transplants between 1 and 7 days after irradiation. While several short-term remissions resulted, all patients died within 1 year of treatment.

This study suggested that total-body irradiation alone could produce short-term remission in some cases of leukemia. Temporary remission in the case of bone marrow transplants, however, was not proof of survival of the transplanted cell. In acute leukemia, the leukemic cells appeared to be radiosensitive, and profound cell destruction occurred after a single large dose of radiation. This study was funded by the U.S. Atomic Energy Commission.

References

Andrews, G.A., B.W. Sitterson, A.L. Kretchmar, and R. Tanida. AStudies of Total-Body Irradiation and Attempted Marrow Transplantation in Acute Leukemia.@Acta Haematalogica. Vol. 26, 1961, pp. 129B153.  "

OR-28. Use of Iodine-130 to Study Thyroid-Stimulating Hormone in Cancer Patients

DURING THE PERIOD from 1965 to 1966, researchers in the Medical Division of the Oak Ridge Institute of Nuclear Studies studied the suitability of iodine-130 (I¹³⁰) as a tool for investigating the effects of thyroid-stimulating hormone on thyroid cancer.

Forty tests were conducted on 18 subjects, including 5 with healthy thyroids and 13 with thyroid cancer. Subjects were administered 0.1 to 5.0 millicuries of I¹³⁰ and were counted to determine thyroid uptake at 4, 24, 48, and 72 hours. Some were also administered thyroid-stimulating hormone by intramuscular injection before or after I¹³⁰. Some received thyroid blocking before or after the administration of the hormone plus I¹³⁰ administration. The uptake of I¹³⁰ in neck lesions associated with thyroid cancer was measured in four subjects after their thyroids had been surgically removed.

The investigators found that thyroid-stimulating hormone did not affect the uptake or distribution of I¹³⁰. This study was supported by the U.S. Atomic Energy Commission.

References

Pfannenstiel, P., B.W. Sitterson, and G.A. Andrews. AIodine-130 for Studying the Effect of Thyroid-stimulating Hormone In Patients with Thyroid Cancer.@Journal of Nuclear Medicine. Vol. 9, 1968, pp. 90B95.  "

OR-29. Study of Uranium Excretion in Urine After Exposure to Uranium Oxide Dusts

IN 1944 TO 1945, a test was conducted at the Y­12 Plant, Oak Ridge to determine the rate of uranium excretion by workers occupationally exposed to uranium oxide dusts. The purpose of this test was to obtain information needed to interpret urinalysis results for workers involved in chemical processing of natural uranium compounds at the Y-12 Plant.

After the average uranium concentrations in urine were determined for a group of 168 chemical production workers, both male and female, from routine occupational exposure to uranium dusts in their work place, a special study was conducted. Two male volunteer workers at the Y-12 plant were deliberately exposed to high concentrations of airborne uranium oxide dust near a dryer in the bulk treatment department. The operator attempted to make the air more dusty (about 28 milligrams natural uranium per cubic meter air) than would otherwise be normal. The subjects inhaled the dusty air for 30 minutes. Twenty-four-hour urine samples were collected prior to the test exposure and for 3 days following to determine the rate of uranium excretion before and after exposure.

This experiment showed that inhaled uranium dust was rapidly excreted and that the maximum rates of excretion occurred within 12 hours of exposure. The Y-12 Plant was operated for the U.S. Atomic Energy Commission.

References

Smith, S.B. AComparison of Job Location with Urinary T Concentration,@and attached memorandum to Dr. Sterner dated September 6, 1945. Oak Ridge, TN: Martin Marietta Energy Systems, Y-12 Plant, (not dated), Health Physics Department, Folder AArchives Files.@

ATwo Experiments of the Excretion Rate of T.@Oak Ridge, TN: Martin Marietta Energy Systems, Y-12 Plant, (not dated), Health Physics Department, Folder AArchives Files.@

ATuballoy in Urine.@Oak Ridge, TN: Martin Marietta Energy Systems, Y-12 Plant, (not dated), Health Physics Department, Folder AArchives Files.@ "

OR-30. Study of the Effects of Beta Rays on Skin Using Phosphorus-32

IN 1945, RESEARCHERS at Oak Ridge National Laboratory conducted an experiment to determine the threshold dose of beta radiation and induced skin reactions. A total of 10 normal, healthy adult volunteers were exposed to between 140 and 1,180 rads of localized external beta radiation to the skin surface from a plastic disk containing phosphorus-32 applied to the skin of the forearm or inner thigh. After exposure, the subjects=skin was monitored at increasing time intervals for a period of up to 8 months.

The results indicated that the threshold dose of beta radiation required to cause mild tanning of the skin is about 200 rads, and for erythema (reddening) is about 813 rads. This research was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Wirth, J.E., and J.R. Raper. AReactions of Human Skin to Single Doses of Beta Rays.@Chapter in Effects of External Beta Radiation, edited by R.E. Zirkel, pp. 193B199. New York: McGraw-Hill, 1951.  "

OR-31. Thyroid Metabolism of Iodine-131 in Single Versus Continual Ingestions

IN THE EARLY 1960s, scientists at Oak Ridge National Laboratory examined the thyroid uptake and bodily excretion of iodine-131 ( I¹³¹) in single and daily administrations to test the theory that I¹³¹ is metabolized in the thyroid at the same rate as stable iodine.

Five male volunteers ingested resin-treated milk containing protein-bound I¹³¹. In the first stage of the experiment, the five received either 0.15 or 1.84 nanocuries of I¹³¹ per day for 4 to 63 days. Thyroid activity in all five subjects was measured with a scintillation counter and urinary excretion was monitored for two of these five.

In a second study, two subjects received a single administration of 92 nanocuries of I¹³¹ and thyroid uptake and urinary excretion were monitored.

The study found that the predicted uptake of I¹³¹ for the single dosages was slightly higher than expected, and that the continued ingestion uptakes came close to matching the predictions. This study was funded by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Bernard, S.R., B.R. Fish, G.W. Royster, L.R. Farabee, P.E. Brown, and G.R. Patterson. AHuman Thyroid Uptake and Bodily Elimination of I¹³¹ for the Case of Single and Continual Ingestion of Bound Iodine in Resin-Treated Milk.@Health Physics. Vol. 9, 1963, pp. 1,307B1,323.  "

OR-32. Study of Decontamination of Skin Contaminated with Silver-110m

IN 1963, a researcher at Oak Ridge National Laboratory conducted a study to determine the depth of chemical penetration into skin by a solution of silver-110m (Ag^110m) in nitric acid, and to evaluate the effectiveness of skin decontamination procedures and materials.

One drop containing 0.2 millicurie of Ag^110m was self-administered by the researcher to the skin of each arm and spread over an area of approximately 0.5 square inch. The skin was blotted and anesthetized, after which a sample of skin tissue was obtained to determine by autoradiography the depth of penetration of the Ag^110m. The area of skin on the other arm was decontaminated several times with detergent and water, and a second biopsy was performed after decontamination to determine by autoradiography the depth of penetration and amount of Ag^110m remaining in the skin. Each of the contaminated areas of skin was counted using a radiation detector to measure the Ag^110m activity present after each procedure.

The study showed that detergent was not effective in removing Ag^110m from the contaminated skin; however, abrasive removal of skin did remove some of the residual activity. This experiment was supported by the U.S. Atomic Energy Commission.

References

Correspondence. G.S. Hill. AHuman Skin Decontamination Study.@Oak Ridge National Laboratory July 25, 1963. Oak Ridge/Energy Systems/ORNL (X­10), Collection Personnel Radiation Records, 1943Bpresent, Dosimetry Data Management.  "