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Health Physics Pergamon Press 1963. \To1 9, pp. 1249-1252. Printed in Northern Ireland THYROIDAL DEPOSITION IN MAN, RAT AND DOG OF New York State Veterinary College, Cornel1 University, Ithaca, New York Abstract-There were no significant differences in the thyroidal uptake of 1131from water solution as compared to 1131from cow's milk in eleven adult human subjects. In rats and dogs it was also observed that there were no differences in thyroidal uptake from water solutions and milk. , In addition, there were no differences in competitive utilization from the two sources between old and young animals and, in rats, between rav and pasteurized milk. IT IS generally accepted that ingestion is the principal mode of exposure to radionuclides produced in the testing of nuclear weapons. Of all the radionuclides produced in these tests, P31 is the only radionuclide which results in a dose to the critical organ of children which is significant when compared to the dose resulting from natural background radiation.(l) I t is also known that in many countries fresh milk is an important source of 1131 for this segment of the population.(2) There are considerable data available on the thyroidal uptake of 1131 by human beings following ingestion of the radionuclide as a water solution or as medical diagnostic capsules. It is important to know whether absorption and retention from such preparations are the same as from 1131ingested by the cow and secreted in the milk. I n the present study the following comparisons between uptake of milk and non-milk radioiodine were made : ( 1) thyroidal uptakes b y eleven normal adults at two different times utilizing external counting of the thyroid gland, (2) thyroidal uptake in rats determined hv removing and analyzing the glands (effects of age of animal and pasteurization of milk \vere studied) and (3) thyroidal uptakes in )-oung and mature dogs using a double tracer technique to give results on the same animal at the same time. * Supported under contract with the U.S. Atomic t Medical aspects under supervision of Dr. P. Studies with man The subjects were eleven male volunteers ranging in age from 26 to 52 years. Each was interviewed by the physician in charge, judged to be clinically euthyroid and warned about taking drugs or eating foods that might affect the results. They were asked to eat a normal breakfast at about 0700 hours and nothing thereafter, were given the dose of radioiodine at about 1000 hours, and ate nothing until lunch about 2 or 3 hr later. The milk was obtained from a dairy cow that had been fed about 2 mc of 11312 days previously. The milk contained about 0.25 ,uc/lOO ml. I t was strained, pasteurized and cooled prior to consumption. The 1131in inorganic form was used as supplied in capsules by a commercial The 1131uptake was measured by adaptation of an inverted ZT, liquid scintillation, wholebody counter.(3) The window and spectral region were arbitrarily chosen to give maximum sensitivity for counting P31, and only the t\vo phototubes which scanned the region of the tank in the area of the thyroid gland were used. A lead shield was devised which covered the head and neck region and reduced the thyroid count to about 5 per cent of the count measured without the shield; the results were corrected accordingly (Fig. 1). No correction was applied for the error introduced by the fact that the shield reduced the contribution from the non-thyroid regions of the head and
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1250 THYROIDAL DEPOSITION IN MAN, RAT AND DOG OF RADIOIODINE Thickness of shield. FIG. 1. Shield used in the Cornell whole-body counter in determining human thyroidal uptake T h e procedure was as follows : (1) The subject drank the milk dose, or swallowed the capsule with about 100 ml water. (2) A sample of the dose solution or a standard capsule was placed in a vial; this was used as a standard in a plastic phantom that simulated the human neck and thyroid gland. (3) At the appropriate times after dosage, the standard was counted for 3-5 min in the same position as the subject. (4) At the appropriate times after dosage, the subject was counted for 3-5 min without the shield and then for 3-5 min with the shield. A typical protocol was as follows: Subject in shield 2373 cpm The administration of 1131 in milk was started for all subjects on January, 28 963. The administration by capsule was started for six of the subjects on February 14 and for the rest on February 25, 1963. Before the start of the capsule experiment, the subjects and milk standards were measured so that corrections could be applied for any residual thyroidal activity from the previous milk study. The animals used were twenty-four albino rats with an average body weight of 216 g, and twenty-four younger rats averaging 58 g. Water containing 1131 was administered via stomach tube to twelve rats per age group whereas the remaining twelve rats in each group received milk from a cow given 1131 16 hr prior to milking. 'l'his milk contained 0.015 pclml and was fed raw to six animals per group and pasteurized to the other six. Two ml of dosing material was fed to each of the older rats and 1 ml to each of the younger rats. After 24 hr the thyroids were removed from the rats, digested in a KOH solution, and counted in a well-type scintillation counter. The animals used were nine mature dogs of mixed breeding, weighing from 12 to 32 Ib, and seven 6-8 week old Beagle puppies weighing from 3 to 4.5 lb. The dogs were fed twice daily, the older animals receiving canned beef, and the puppies canned beef and milk. This study involved a double isotope technique. The dogs were fed by stomach tube; some received milk containing 1131 and others water containing 1125. Six hr later these dogs were given the alternative dosing material. One adult dog and one puppy were fed water containing 1131,followed 6 hr later by 1125 in water in order to check the relative recoveries of the two radionuclides. The milk used contained 48 hr after oral ingestion of 1131 as NaI. The tlvo water solutions contained 0.02 pclml of P5and of 30 ml for the larger dogs and 20 rnl for the puppies. O n the day of the experiment a partial meal of beef was fed 3 hr after each dose After 6 days, the thyroids of the dogs \yere removed, digested with a KOH solution and counted against standards containing the same concentration of KOH. Counting was done at the appropriate peaks for each radionuclide in a well-type scintillation detector attached to a single channel analyzer. The percentage uptakes of both nuclides were then calculated. RESULTS AND DISCUSSION The data for the human subjects are presented in Table 1. Values are given for thyroidal uptakes at 6, 24, 48 and 168 hr. ;is expected from patterns of 1131 metabolism, the absolute values at 6 hr were lokver than those at
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Table 1. Per cent thyroidal uptake in man of S3'from water and milk Subject Water Milk Diff. Water Milk Diff. Water Milk Diff. Water Milk Diff. the later times, although not as low as usually cited in the textbook^;(^^^) no differences were observable between the 24, 48 and 168 hr values. Although the number of subjects in this study is too small to permit broad generalizations, it is of interest to note that the average uptake values were much closer to 20 per cent than to the 30 per cent value now recommended for health physics consideration^.(^.^) The primary purpose of this study however, was the comparison between water and milk sources of radioiodine. The average Il3' uptake from milk was 6-13 per cent higher than from sistently favouring uptake from milk, two were equivocal and two consistently favored uptake from water. The use of paired t-tests for each time period, however, revealed no significant Table 2. Thyroidal uptake in rats of from milk and water 24 hr after ingestion Weight group Water * Sample standard error.
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1252 THYROIDAL DEPOSITION IN MAN, RAT AND DOG OF RADIOIODINE differences in 1131 uptake from the water and milk (0.01 level of significance). The 24-hr values for thyroidal uptake of 1131 in rats are presented in Table 2. Statistical analysis of the data showed no significant difference in thyroidal uptake between rats fed iodine in water or in milk, or between those fed iodine in raw or in pasteurized milk. The most precise comparison of uptakes from milk and non-milk sources should be possible from double tracer techniques since all biological variability is theoretically eliminated. The design of the dog experiment was based on previous knowledge of 1131 metabolism.(s) It was considered that a 6-hr interval between administration of the doses would avoid any interaction in the gastrointestinal tract. The animals were killed at 6 days after dosage since at that time the radioiodine retention curve is essentially level and the 6-hr time difference in administration of the dosages would not have any effect. As a check on the experimental plan three studies were made : ( 1) in some of the dogs the water dosage was given first and the milk dosage 6 hr later, (2) in other dogs the order was reversed and (3) some dogs were given both the 1131 and 1125 in water solution. The data from the dog experiment are presented in Table 3 and are expressed as ratios uptake in thyroid from milk dose . Ten of Of uptake in thyroid from water dose the dogs showed a slightly greater uptake of radioiodine from milk, two showed no difference, and two had a slightly greater uptake from water. Any possible significance is obscured, however, because the two dogs receiving both radionuclides in water showed a slightly greater uptake of the 1131as compared to 1125. I t appears that the differences, if any, are very small and of no practical import. 1. E. B. LEWIS,Proc. Nat. Acad. Sci. 45, 894 (1959). CISCO-A whole body counter f o r man and domestic animals, in press. 4. S. SILVER,Radioactive Isotopes in Medicine and Biology (2nd Edition). Lea and Febiger, Phiiain Clinical Research and Diagnosis. Butterworth, 6. Federal Radiation Council, Report No. 1. U.S. Government Printing Office, Washington, D.C. (1960). 7. Federal Radiation Council, Report No. 2. U.S. Government Printing Office, Washington, D.C. (1961). Amer. J . Vet. Res. 23, 412 (1962). Table 3. Relative thyroidal uptake in dogs of radioiodine from milk and non-milk sources* -\verage of treatments I and I1 1.06 1.04 uptake of 1131 from milk uptake of 1131 from water uptake of 1125 from water as control of technique).