List of Experiments

Brookhaven National Laboratory

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

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

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

References

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

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

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

BNL-2. Boron Neutron Capture Therapy

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

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

References

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

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

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

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

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

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

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

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

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

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

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

References

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

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

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

References

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

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

References

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

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

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

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

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

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

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

References

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

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

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

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

BNL-9. Metabolic Studies with Manganese-54

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

References

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

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

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

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

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

References

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

References

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

 ‡  ‡  ‡

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

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

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

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

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

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

References

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

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

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

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

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

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

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

References

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

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

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

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

References

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

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

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

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

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

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

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

References

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

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

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

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

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

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

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

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

References

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

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

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

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

References

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

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

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

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

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

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

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

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

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

References

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

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

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

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

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

References

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

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

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

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

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

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

References

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

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

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

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

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

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

References

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

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

BNL-38. Metabolism of Zinc-65

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

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

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

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

References

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

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

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

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

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

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

References

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

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

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

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

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

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

References

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

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

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

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