Proceedings of the 12TH Annual Bio-Assay and Analytical Chemistry Meeting - Metabolic Data on Injected and Ingested Thorium-234 in Human Beings (Partial)

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METABOLIC DATA ON INJECTED AND of the 12th Annual held at Gatlinbuyg, Tennessee

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METABOLIC DATA OW INJECTED AND INGESTED 234Th ~ ssa chu sett eInstitute o f Technology ~n the couree o f an experiment to determine the relative absorption of Ra and Th from the gastrointestinal t r a u t of normal human beings, information on the meta bol hm of soluble 23% after intravenous injection, and on the metabolism of 23%!h(S0*)~ after oral administration has been obtained, Five elderly hwnan subjeate, 3 males and 2 females, w e r e injected intravenoucsly with carrier-free 23%h i n isotonic include radioactivity measurements on blood, urine, and feces, as w e l l as whole-body 7-ray measurements (chair and scan), and partial body (upper 2094, including head and arms) measurements using a new "Eskull and crossbones" (SXB) position, by means of Bioassay techniques used in the metabalfc studies . which the gaatrointe6tinal tract i a shielded with Bb. ' Whole body retention of Th is - 96% a t 1 day', - 94% at 5 days, and -9096 at 2 months, the Th being excreted mainly in . *This work was supported in part by the Division o f ~iologya d ' 'Present addsass: Cancer Research Xnetitute, New England Deaconess Hospital and Dept- of Legal Medicine, €Iarvard Medical School, Boston, Masaachusetta. from Radiation Bio - Effects Program, lational Center for Radiological

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JUN 22 '94 1 4 : O l INEL TECH LIBRARY -12 for males and - 2 4 for females. The SXE3 measurements also indicate tt sex difference, the amount of Th measured in the upper 2096 o f the body for the females being ~1.6 t b e s greater than that for the males. Total blood retention o f Th is N 10% at 1 day, - 1% at 5 days, and ~ 0 . 3 %at 10 days. The cumulative urine-to-feces ratio a t 5 days is A second group of elderly subjects, 3 mles and 3 females, were administered orally late original Rn dial paints. i n the metabolic atudies after injection of 234Th, which provided calibration data for the absorption stud be, were used to determine the transport o f 23%h across the gut wall, The average value for fractional 234Th transport is 5 0 , 0 0 0 3 , the mast probable value being 0,0002. Individual values range from 0.0001 to 0.0006. Cumulative fecal excretion o f 234Th I s >98% of the admbistesed dose for 4 subjects, and ~ 9 0 %for the remaining 2 subjecttt, at 4 days. Whole body y measurements Show that cumulative excretion at 8 days is jects and -9896 for 1 subject. The same bioassay techniques used The implication8 o f these findings to the internal dosimetry and radiation protection guidea f o r thorium in man are discussed. Metabolic Data on Injected and Ingested 234Th in Human Beings Information on the metabolism o f thorium by human beings is essentially non-existent. what information is available had been obtained from studies on human subjects with long ten burdens of Thorotxast. The metabolism of t h i s colloidal material can be considerably different f+om thorium ion or thorium complex &on and can be inapplicable to the assessment of internal radiation dose for radiation protection purposes. In carrying out an experiment on the relative absorption of radium and thorium on human subjects (l), it was necessary to obtain calibration information by injecting human subjects w i t h thorium. Some of these results are directly applicable to the metabalfam of thodam in humn beings. These results, along with the resulta of an experiment on the absorption o f

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thorium, are presented here hi a form useful fox bioassay needs, and are the first, to our knowledge, relating t o the metabolism of thozium in man. Po# studies in human subjects 234Th i s the best choice since other thorium isotopes have elither half-periods which are too short or have longer half-periods and hence produce a larger internal radiation dose. longer than that of 23%!hwould be desirable f o r longer term studies, but this is not possible and there is little choice An isotope with a half-period Carrier-free 234Th is prepared by solvent extraction and tained from melts in graphite crucibles. F o r injection purposes the Th is converted to citrate at pH 3.5 and prepared ina way to yield a sterile and pyrogen-free product. tration, a mock radium d i a l paint containing both 23% and 224Ra 5.s prepared by an adaptation o f a method developed by Stover (2) The adaptation is concerned with the preparation of a single dose at: one t h e , and the result is Th (SO,$2 and RaSO4 carried on Bas04 intimately mixed i n ZnS phosphor. contained i n a gelatin capsule fox administration. The dry mock paint is Standardization of the 234Th activity is carried out against spectroscopically pure u308 by comparing the gamma spectrum from a 234Th citrate 60luCton and that of a solution of u308 dksolved period o f 4 . 5 1 x 10% and its abundance of 99.3% (3). Standardization of 23%h i n the mock radium dial paint is made b first the mock paint containing both nuclides. 234!Ch determined during.the experiment i s consistent with the The activity of the 23%7 i s calculated fx omits halfstripping the spectrum of mock paint containing only 22xRa from Figure 1 shaws a gamma spectrum of 234Th. The 1.00 MeV gamma ray gives a better signal t o noise ratio than does the combination o f 0.77-1.00 MeV and is used for standardization purporres and for several other measurements. The lower energy gamma rays (64 and 93 keV) are u s e f u l because of their 10-fold greater abundance even though greater self-absorption requires more careful experimental control.

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Body y countkg is carried out i n the controlled background Whole body meaaurernmts are also made with facility or whole body counter described in the IAEADbectory ( 5 ) tilting metal chair. the arc method developed by Evans ( 6 ) , using an arc of 1.25 meters. The reproducibility o f these two whole-body counting methods is Standard chair measurements are made using a Since. wh le body y counting of subjects after ozal administinal tract, and shce the absorption of 234Th was anticipated

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to be very Xaw, a new partial body counting position was devised. The "skull and crossbone8" (SXB) method i s a body counting technique by which measurements of body burden are made from the unshielded upper ( r ~ )20-2596) part of the body, while the (3.X. t r a c t and the lcrwer part of the body are shielded from the detector. o f 234Th i n the body are minimized by measuring as much of the' in the SXB position. and is pushed forw&d so that the chest is against the Pb shield, which consists of a 12" x 12" x 12" stack o f bricks, an additional layer of two bricks (8" x 8" x 2") and second layer o f one brick. The subject's am8 embrace the 8" x 8" layer, w i t h the chin foam 2.5 in. thick) attached to the crystal serves t o maintain a fixed distance from the cryrital face to the nasion. Thus, the eefects of variable distribution The subject sits on an adjustable chair - The sensitivity and reproducibility of the method were checked using human subjects (Ra dial painters, Radithor drinkers, etc.) whose Ra and Th body burdens were measured w i t h the chair and/or arc method. The results indicate that the effects of repositioning are sufficiently small t o be considered h sign if i - cant, and t h a t the efficiency for determination of body burden i s comparable to that of the standard chair position. Phantom studies indicated Chat a residual 1wCi 234Th i n the G.I. tract would not be interpreted asa significant body burden, and also indicated t h a t the measurement of an expected transport of log4 across the gut wall would require the oral administration of at least 100 pci 234Th, using the 64 and 93 keV 23%h y rays (49-116 keV) are denoted by the code 'ILOSXBvl, w h i l e those using the 1.0 MeV 2 3 4 m ~ ay ray (0.9-1.1 MeV) are denoted by the code "H8SXS1'- Scan measurements are made w i t h the subject lying supine or prone on a table 30 cm. below the face of the crystal. crystal is tracked at a constant rate over a distance of 75 in. along the midline of the subject's body. rates are low live-time control of the scan is not necessary and the counting r a t e is determined from the total. counts divided by the counting period. Since the counting Twenty-four hour urine and feces samples are collected i n . individual 2 liter polyethylene bottles, preserved with -3,

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and made t o volume. The-gamma activity of these samples is compared to that of standard solutions of the same volume. Blood samples are drawn in heparinized plastic disposable The ash is .syringes. Aliquots are dried i n porcelain crucibles and ashed, the Fe in blood acting as a carrier f o r the 234Th. taken up i n HPJO3, transferred to planchet6 and counted in alaw background proportional flow counter.

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Control samples were obtained f r o m each subject and control measurements were made on the subjects prior to the start of t h e Healthy male and female subjects, ranging i n age from 63 All underwent at o 8 3 years, volunteered for the experhent. complete history and physical examination, and were required t o be free from any renal or G.1. disease, any endocrine o r metabolic disease, any serious recent illness, any skeletal disorders, or unusual dietary or bowel habits. Clinical laboratory studies were conducted and x-rays of the long bones and skull were taken. injection or ingestion studies, but no individual was used in both. During the experiment the subjects were housed for the collection of excretion samples and a trained nurse was in attendance t o insure that no inadvertent contamination occurred during t h e collection of excretion samples. The subjects.participated either in the Injection of 234Th citrate is made i n an antecubital vein. The activity administered is determined by measurements on the syringe contents before and after administration. administration of 234Th and 224Ra mock radium dial paint is made by mallawing the gelatin capsule, using water i n several steps, to insure that the capsule enters the stomach. 5s verified with a survey meter. Table.1 shows some of the physical characteristics and the dgse schedule for each subject. The calibration factors (net cpm/pCi retained) for the chair, H~SXB,and L8SXB p8itbns are shown i n Fig. 3. The retained body burden i s calculated from excretion data. The chair calibration shows a decrease of -20% over the first two days then remains constant a t (80 & 3%) cpm/yxli retained Over the 24 day observation period, w i t h no significant difference between males and females. fn contrast t o the chair results, the calibration for the #8S= position shows a 10-3054 increase during t b first 'day. The. calibration factors for the H8SxEI and L8SXB positions show a difference between the sexes, with the females having the higher values. For the H8SXB position, the average value for the females is (80 & 3%) cpm/pci, and for the raftles (50.2 4%) cpm/pCi. The respective values for the L8SXB position

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it is concluded that 234Th and 234Pa are present i n the Same ratio in both males and females, at least -in the upper 20-25s of.the However, since the ratio NO reason i s known for the apparent difference in distribution of 234Th between males and Eemales, a difference which might be expected to manifest itself in the chair measurements, but which does'not. Arc measurements made w i t h pb bricks shielding the body from just above the sternum to the h i s, and conducted to detamrine whether a significant excess of 294Th was present in the liver, indicate no excess in this region (average counting rate with shield is 75% of counting rate without shield) with no significant difference between males and females. The excretion data are given in Table 11. The total excretion of 5 ~ 6 %h 5 days indicates that the excxetion of 23%!h i s Low. The excretion is predominantly by the urinary route as shown by the high cumulative urine to feces ratio of -12 for males and -24 for females. The two values in t h i s ratio become a second point of difference between the mxes but it i s not knwn whether this difference is related to khe sex difference SXS calibration. The daily urinary excretion of'@hl!h i s not proportional to the amount o f 234Th in the blood, as shown in served in the The curves appear to meet at the end of the experimental

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* period, but whethez they continue parallel to each other or cross is unknown at this the. Whether the rea8on for this nonproportionality is due to an increase w i t h t h e or to an exchange of !L% between plasma and red cells or to other factors is also unknown at thia time. the Th plasma clearance The retention results axe given in Pig, 4, The results are a composite of excretion measurements and of moaap-renaents made with the chaiig and L8SXB positions. -93% at 20 d and thgn changes very sluwly through the 100-day observation period, Efforts to calculate the long-term disappearance rate are shown in Table I11 as,sums of exponential terns The retontion drops to

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JUN 22 '94 14:06 INEL TECH LIBRARY and as a power function. accurately a long half-period from a short-term experiment, the best indication from the present results i s that the half-period is probably > 5 years. While it is dLfficult to determine Figure 5 shows the results on the blood measurements expressed a8 a percentage of the administered dose in the s s t i - mated whole blood volwne, there being no convenient way to express a thorium specific activity. The blood activity is -10% shape of the 234Th blood curve i s similar to the curve in human beings (l), but the absolute levels of 23%h i n blood are about 10 times higher. at 1 day and -0.3% at 10 days. For comparative 3;;Pg-;-&h' . The scasl data, plotted as net cpm/pCi retained 10 days after ratio, are shown in Fig- 6 . activity of the prone scan i s The results indicate that the -15% greater than that of the

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supine, perhaps due to 23- deposition i n the skeleton. scan measurements are somewhat less sensstive …