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Radiation dosimetry of Adrenal imaging agents 19-iodocholesterol and 6-iodomethylnorcholesterol
l n l e r n a l i o n a l J o u r n a l of A p p l i e d R a d i a t i o n a n d I s o t o p e s , Vol. 29, pp. 277 279 © P e r g a m o n Press. Ltd,. 1978. P r i n t e d in G r e a t B r i t a i n
(~)20-708X 78 0501-0277S02.00 0
Radiation Dosimetry of Adrenal Imaging Agents 19-Iodocholesterol and 6-Iodomethylnorcholesterol VALERIE ANNE BROOKEMAN University of Florida College of Medicine and Veterans Administration Hospital. Box J-385, JHM Health Center, Gainesville, FL 32610, U.S.A.
{Received 23 September 1977) Radiation internal absorbed doses to seven organs are calculated for adrenal imaging radiopharmaceuticals, 19-iodocholestrol and 6-iodomethylnorcholesterol labeled with 13~i or 1231, from published biological distribution data of the ~2SI-labeled compounds of greater than 980,~,chemical purity. Consideration of the biological distribution, dosimetry and physical data indicates that ~231-6-iodomethylnorcholesterol is preferred for adrenal scintigraphy.
1. I N T R O D U C T I O N
2. M A T E R I A L S
SINCE its synthesis in 19704~, radioiodinated 19-iodocholesterol has been investigated and utilized as a radiopharmaceutical for imaging the adrenal glands. 42-s~ In 1975 an isomeric impurity in 19-iodocholesterol, 6-iodomethylnorcholesterol, was identified 46) and confirmed. (7~ The concentration in the adrenals of the "impurity", 6-iodomethylnorcholesterol, was subsequently reported to be greater than that of 19-iodocholesterol by a factor of 5-10, (8'9) hence indicating its superiority as an adrenal imaging agent. The synthesis of gram amounts of 19-iodocholesterol (~°) and 6-iodomethylnorcholesterol(~) in greater than 98% chemical purity and greater than 99% radiochemical purity and their distribution in rats 4~2) have recently been reported. From the published distribution and clearance data, (~2) estimates of radiation absorbed dose to humans are presented for "'pure" 19-iodocholesterol and "pure" 6-iodomethylnorcholesterol labeled with 1311 or 123I.
AND
METHODS
The tissue distribution data utilized for the radiation absorbed dose estimates are extracted from the paper of COUCH and WILLIAMS, (12) where details may be found. Hence only a summary will be presented here. 70/aCi (0.2 mg in 0.2 ml) of "pure" 125I-6-iodomethylnorcholesterol or ~251-19-iodocholesterol were injected through the tail vein of mature SpragueDawley rats weighing 400--450 g. Lugol's iodine was not administered. Whole organs, excised at 1, 3 and 7 days post injection, were weighed, counted in an automatic gamma well counter and, following correction for ~25I-decay, converted to percentage of injected dose/g in order to facilitate comparison with the distribution data of earlier preparations, la'9~ However, for the purposes of determining radiation dose estimates these biological distribution data were converted back to percentage of injected dose/whole organ and are presented in Table 1, where each point represents the mean of three rats.
TABLE 1. Biological distribution in rats of 1 2 5 l-6-iodomethylnorcholesterol t 251.19_iodocholesterol Injected
Do~e/~4hol~ O r g a n ( s . d . )
,,- I,,,]~, nt t hv ln~,r t h o l c : ; l ,.r,,1 Tissue
ha) 1
(0.2)
19- h~(h~ch;,], ~ t t,r,, 1
Day 3
2.6
40.4)
Day 7
2.6
Day i
41.6)
0.09
40.04)
Day 3
0.05
(0.02)
Day 7
Adrt'n:,l
t.6
Thyroid
0.9 (0.2)
1.6 (0.2)
0.9 (O.l)
2.4 (0.9)
4.5 (l.t)
0.07
3.7 (3.1)
(0.02)
Liver
].4 (0.3)
0.9 (0.2)
O.31 (0.09)
0.31 (0.08)
0.08 (0.02)
0.02 40.01)
Kid,ley
0.41 (0.02)
0.34 (0.06)
0.23 40.07)
0.12 (0.01)
0.04 (0.01)
0.01 (0.001)
Tt,~t~s
0.12 (0.03)
0.13 (0.02)
0.09 (0.04)
0.06 (0.002)
0.02 (O)
0.005 (0)
Spleen
0.80 (0.09)
0.43 (0.]0)
0.[4 (0.03)
0.20 40.05)
0.03 40.003)
0.005 (O)
Lung
0.85 40.09)
0.59 (0.22)
0.30 (0.12)
0.17 (0.02)
0.04 (0.0])
0.01 (O)
Bh,od
14.4
7.9
2.7
5.2
1.2
0.2
277
and
278
Valerie Anne Brookeman
TABLE2. Radiation absorbed dose (rad/mCil from adrenal imaging agents Target
1311_6_iodomethyl_ norcholesterol
1311_19_iodo_ cholesterol
1231_6_iodomethyl_ norcholesterol
123l_12_iodo_ cholesterol
Adrenals
200-203
5.8
1,3
Thyroid
42-61
172-217
0.58
1.5
0.63-0.78
0.09-0.11
0.025
0.0061
Kidneys
1.3-1.6
0.14-0.19
0.034
0,0087
Testes
2,9-3.9
0.59-0.67
0.050
0.024
Spleen
2.0-2.5
0.31-0.34
0.078
0.019
Lungs
0,61-0.77
0.I0-0.12
0,020
0.0051
Liver
Appropriate decay factors for 131I or for 123I were applied to the biological data in Table 1 to yield effective (physical plus biological) clearance data which were used as input to a computer program recently developed for determining internal radiation absorbed dose. t~3. ~4~ The program employs the methodology formulated by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicinetl 5.16) to determine radiation absorbed dose to a target organ from a radionuclide distributed within several source organs. Stored tables of S-factors, the absorbed dose per unit cumulated activity, for selected radionuclides and organs ~16'lv~ are utilized and the total cumulated activity in the various source organs is determined for complete elimination of the radiopharmaceutical by graphic integration of the input effective clearance data. Decisions are made regarding effective uptake of the radiopharmaceutical and the clearance data are extrapolated to infinity assuming either continued effective clearance or physical decay after the last datum point. The tissues listed in Table 1 were used as eight source organs. Blood was considered a source by assuming it uniformly distributed throughout the total body and utilizing total body S-factors. 3. R E S U L T S A N D D I S C U S S I O N The mean absorbed doses for seven target organs are given in Table 2 for the two pharmaceuticals hypothetically labeled with 131I or ~23I. The range of dose estimates for the 13q-labeled compounds represents the two alternatives in extrapolating to infinity for the determination of total cumulated activity; assuming either only physical decay of ~3~I after the last datum point (the higher dose estimate) or continued effective (physical plus biological) clearance as measured at the last datum point (the lower dose estimate). No such ranges appear for the ~23I-labeled compounds since, due to its short physical half-life, both methods of extrapolation to infinity give the same result. The 13q-labeled compounds result in much higher doses (by factors of 15-150) than their equivalent lZ3I-labeled compounds due to the unfavorable
0.070
characteristics of 1311 (beta minus decay and 193 hr half-life) compared with 123I (electron capture decay and 13 hr half-life). As seen by the biological distribution data in Table 1, as much as 60 times (at 3 days after administration) 6-iodomethylnorcholesterol as 19-iodocholesterol accumulates in the rat adrenals. Labeled 19-iodocholesterol, when prepared in >98°; chemical purity according to the method of COUCH and associates, ~1°~ is not taken up sufficiently by the adrenal glands to e'nable their visualization by scintigraphy up to 9 days after intravenous administration,C12~but 6-iodomethylnorcholesterol, when prepared in >98~o chemical purity according to the method of SCOTT and associates ul~ provides satisfactorily high adrenal uptake for imaging from 24 hr up to 7 days after injection. Comparison of the doses in Table 2 from 6-iodomethylnorcholesterol and 19-iodocholesterol with the same radionuclide tag indicate a much higher adrenal dose per mCi (by a factor of 20-35) from the former due to its much more preferential localisation in the adrenals (see Table 1) and a much higher thyroid dose (by a factor of 3) from the latter. Comparison of the radiation absorbed dose estimates presented in this report with earlier published dose estimates reflects the differences in chemical purity, and hence tissue distribution, of the pharmaceuticals. Previous radiation absorbed dose estimates for 311-19-iodocholesterol ~1s-.2o~ utilize biological distribution data from dogs and humans of 1311-19-iodocholesterol prepared by the method of COUNSELL et al/1~ and subsequently shown to contain the isomer. 6-iodomethylnorcholesterol as an impurity in amounts ranging from 10-60')~/° 9.~z~ As Table 1 indicates, "'pure" 19-iodocholesterol has very low adrenal uptake (0.09~o of injected dose at day 1) compared with that of the impure compound (0.4'~"o adrenal uptake of administered activity)/2°~ The resulting adrenal dose for the impure ~311-19-iodocholesterol, 30rad/mCi, ~2°~ is therefore greater than that for "pure" 1311-19-iodocholesterol, 5.8rad/mCi (Table 2). Reported radiation absorbed dose estimates for 311_6.iodomethylnorcholesterol12~ utilize biological
Radiation dosimetry of adrenal imaging agents
distribution data from rats, dogs and humans of 1311.6.iodomethylnorcholesterol prepared by the method of BASMADJIAN et al. 17~ and subsequently shown to be 75-90% pure. t12~ Radiation dose estimates for l 3 ll-6-iodomethylnorcholesterol were reported as 140 rads/mCi to the adrenals and 160 rad/ mCi to the thyroid t21~ from tissue distribution data in rats, where 2.0 and 6.5~o of the administered dose were present in rat adrenals and thyroid respectively at day 1, and 1,7 and 2.1°,~,, respectively, at day 5. tzl) Table 1 shows 1.6 and 0.9% uptake at day 1 in rat adrenals and thyroid respectively, 2.6~'0 adrenal uptake at 3-7 days, and radiation absorbed dose estimates (Table 2) of about 200 and 50rad/mCi to adrenals and thyroid, respectively. The higher adrenal dose estimate for 13q-6-iodomethylnorcholesterol prepared by the method of SCOTT et al. t~x~ reflects its higher and more prolonged adrenal uptake. Thyroid uptake is correspondignly less, and the radiation dose, preferably, lower. The limitations and assumptions of radiation absorbed dose estimates using animal tissue distribution data are obvious. However, the current interest in the preparation of an adrenal imaging agent of high purity 122~warrants the use of the limited existing animal data 112~ for the dose estimates presented here, until human distribution data are available. Additionally, comparison with the radiation dose estimates for the other methods of preparation of 19-iodocholesterol and 6-iodomethylnorcholesteropl8 21) are facilitated since there too animal distribution data were employed. The following additional observations can be made from the results in Table 2 and consideration of the physical properties of 123I and 131I. The frequencies of occurrence of the useful 159 and 364 keV gamma rays from lZ3I and 131I are almost identical, 0.835 and 0.833 per disintegration, respectivelyJ 23~ For the same radiation dose to the adrenal glands, the ~z3I-compound can be administered approximately 150 times more active than the same compound labeled with 13tI, in which case, at 24 or 48 hr after administration the number of useful photons from the ~23I-labeled compound will still be 45 or 14 times, respectively, that from the 13q-labeled compound. For the same radiation dose to the adrenals, the photon flux will be higher, and therefore image quality better, for the x23I-compound rather than the same compound labeled with lalI, up to 100hr after administration. Alternatively, for the same number of useful gamma rays at 24 or 48 hr after administration, 3 or l l times, respectively, more of the shorter-lived 123I-labeled compound would have to be administered than the long-lived ~31I-eompound. However. the radiation dose to the adrenals from the 123I-compound would still be only 0.02 or 0.07 that from the 13q-compound. Finally, the lower energy gamma rays from 12aI are easier to collimate than the high energy gamma
279
rays from 131I and existing commonly-used collimators for 99mTc (140keV gamma rays) can be employed, In conclusion, consideration of the biological distribution, dosimetry, and physical data of 6-iodomethylnorcholesterol and 19-iodocholesterol tagged with 123l or 131I indicates that ~23I-6-iodomethylnorcholesterol prepared in >98°,o purity is preferred for adrenal imaging. Acknowledgements--Thanks are due to MARGARET W. COUCH for supplying the rat distribution data for the ~ZSl-labeled compounds, and to LAWRENCET. FITZGERALD for assistance in running the computer programs.
REFERENCES 1. COUNSELL R. E., RANADE V. V., BLAIR R. J., BEIERWALTES W. H. and WEINHOLD P. A. Steroids 16, 317
(1970). 2. BLAIR R. J., BEIERWALTES W. H., LEIBERMAN L. M.. BOYD C. M., COUNSELL R. E., WEINHOLD P. A. and VARMA V. M. J. nucl. Med. 12, 176 (1971). 3. BEIERWALTESW. H., STURMAN M. F., RYO U. and ICE R. D. J. nucl. Med. 15, 246 (1974). 4. FORMAN B. H., ANTAR M. A., TOULOUKIAN R. J., MULROW P. J. and GENEL M. J. nucl. Med. 15, 332 (1974). 5. HERWIG K. R. and SCHTEINGART D. E. J. Urol. I l l ,
713 (1974). 6. KOJIMA M., MAEDA M., OGAWA H., N1TTA K. and Iro T. J. chem. Soc. Comm. 1975, 47 (1975). 7. BASMADJ1ANG. P.. HETZEL K. R., ICE R. D. and BEIERWALTESW. H. J. labelled Compd. II, 427 (1975). 8. KOJIMA M., MAEDA M., OGAWA H., NITTA K. and ITo T. J. nucl. Med. 16, 666 (1975). 9. SARKAR S. D., BEIERWALTES W. H., ICE R. D., BASMAD-
JIAN G. P., HETZEL K. R., KENNEDYW. P. and MASON M. M. J. nucl. Med. 16, 1038 (1975). 10. COUCH M. W., SCOTT K. N. and WILLIAMS C. M. Steroids 27, 451 (1976),
11. SCOTT K. N., COUCH M. W., MARECI T. H. and WILLIAMSC. M. Steroids 28, 295 (1976). 12. COUCH M. W. and WILLIAMSC. M. J. nucl. Med. 18, 724 (1977). 13. BUTLER P. F., FITZGERALD L. T., VANEK K. N. and BROOKEMANV. A. Radiopharmaceutical Dosimetry Symposium, HEW Publ. 76-8044, p. 127, Bureau of Radiol.
Health, Rockville, MD (1976). 14. BUTLER P. F., FITZGERALD L. T., BROOKEMAN V. A. and VANEK K. N. HIth Phys. 33, 459 (1977).
15. LOEVINGERR. and BERMANM. MIRD Pamphlet No. 1, J. nucl. Med. Suppl. No. I, 7 (1968). 16. SNYDERW. S., FORD M. R., WARNERG. G. and WATSON S. B. MIRD Pamphlet No. II, Soc. Nucl. Med., New York (1975). 17. SNYDER W. S., FORD M. R., WARNER G. G. and WATSON S. B. Oak Ridge National Laboratory Rep.
ORNL-5000 (1974). 18. KIRSCHNER A. S.. ICE R. D. and BEIERWALTES W. H. J. nucl. Med. 14, 713 0973). 19. BLAU M. J. nucl. Med. 16, 247 0975).
20. KIRSCHNERA. S., ICE R. D. and BEIERWALTESW. H. J. nuel. Med. 16, 248 (1975). 21. ICE R. D., Kmcos L. T., COFFEr J. L.~ WATSON E. E., BEIERWALTES W. H. and SARKAR S. D. Radiopharmaeeutical Dosimetry Symposium, HEW Publ. 76-8044, p.
246. Bureau of Radiol. Health. Rockville, MD (1976). 22. SCOTT K. N., COUCH M. W., MARECIT. H. and WILLIAMSC. M. J. nucl. Med. 18, 492 (1977). 23. DILLMANL. T. MIRD Pamphlet No. 4, J. nucl. Met/. 10, Suppl No. 2, 5 (1969).
(~)20-708X 78 0501-0277S02.00 0
Radiation Dosimetry of Adrenal Imaging Agents 19-Iodocholesterol and 6-Iodomethylnorcholesterol VALERIE ANNE BROOKEMAN University of Florida College of Medicine and Veterans Administration Hospital. Box J-385, JHM Health Center, Gainesville, FL 32610, U.S.A.
{Received 23 September 1977) Radiation internal absorbed doses to seven organs are calculated for adrenal imaging radiopharmaceuticals, 19-iodocholestrol and 6-iodomethylnorcholesterol labeled with 13~i or 1231, from published biological distribution data of the ~2SI-labeled compounds of greater than 980,~,chemical purity. Consideration of the biological distribution, dosimetry and physical data indicates that ~231-6-iodomethylnorcholesterol is preferred for adrenal scintigraphy.
1. I N T R O D U C T I O N
2. M A T E R I A L S
SINCE its synthesis in 19704~, radioiodinated 19-iodocholesterol has been investigated and utilized as a radiopharmaceutical for imaging the adrenal glands. 42-s~ In 1975 an isomeric impurity in 19-iodocholesterol, 6-iodomethylnorcholesterol, was identified 46) and confirmed. (7~ The concentration in the adrenals of the "impurity", 6-iodomethylnorcholesterol, was subsequently reported to be greater than that of 19-iodocholesterol by a factor of 5-10, (8'9) hence indicating its superiority as an adrenal imaging agent. The synthesis of gram amounts of 19-iodocholesterol (~°) and 6-iodomethylnorcholesterol(~) in greater than 98% chemical purity and greater than 99% radiochemical purity and their distribution in rats 4~2) have recently been reported. From the published distribution and clearance data, (~2) estimates of radiation absorbed dose to humans are presented for "'pure" 19-iodocholesterol and "pure" 6-iodomethylnorcholesterol labeled with 1311 or 123I.
AND
METHODS
The tissue distribution data utilized for the radiation absorbed dose estimates are extracted from the paper of COUCH and WILLIAMS, (12) where details may be found. Hence only a summary will be presented here. 70/aCi (0.2 mg in 0.2 ml) of "pure" 125I-6-iodomethylnorcholesterol or ~251-19-iodocholesterol were injected through the tail vein of mature SpragueDawley rats weighing 400--450 g. Lugol's iodine was not administered. Whole organs, excised at 1, 3 and 7 days post injection, were weighed, counted in an automatic gamma well counter and, following correction for ~25I-decay, converted to percentage of injected dose/g in order to facilitate comparison with the distribution data of earlier preparations, la'9~ However, for the purposes of determining radiation dose estimates these biological distribution data were converted back to percentage of injected dose/whole organ and are presented in Table 1, where each point represents the mean of three rats.
TABLE 1. Biological distribution in rats of 1 2 5 l-6-iodomethylnorcholesterol t 251.19_iodocholesterol Injected
Do~e/~4hol~ O r g a n ( s . d . )
,,- I,,,]~, nt t hv ln~,r t h o l c : ; l ,.r,,1 Tissue
ha) 1
(0.2)
19- h~(h~ch;,], ~ t t,r,, 1
Day 3
2.6
40.4)
Day 7
2.6
Day i
41.6)
0.09
40.04)
Day 3
0.05
(0.02)
Day 7
Adrt'n:,l
t.6
Thyroid
0.9 (0.2)
1.6 (0.2)
0.9 (O.l)
2.4 (0.9)
4.5 (l.t)
0.07
3.7 (3.1)
(0.02)
Liver
].4 (0.3)
0.9 (0.2)
O.31 (0.09)
0.31 (0.08)
0.08 (0.02)
0.02 40.01)
Kid,ley
0.41 (0.02)
0.34 (0.06)
0.23 40.07)
0.12 (0.01)
0.04 (0.01)
0.01 (0.001)
Tt,~t~s
0.12 (0.03)
0.13 (0.02)
0.09 (0.04)
0.06 (0.002)
0.02 (O)
0.005 (0)
Spleen
0.80 (0.09)
0.43 (0.]0)
0.[4 (0.03)
0.20 40.05)
0.03 40.003)
0.005 (O)
Lung
0.85 40.09)
0.59 (0.22)
0.30 (0.12)
0.17 (0.02)
0.04 (0.0])
0.01 (O)
Bh,od
14.4
7.9
2.7
5.2
1.2
0.2
277
and
278
Valerie Anne Brookeman
TABLE2. Radiation absorbed dose (rad/mCil from adrenal imaging agents Target
1311_6_iodomethyl_ norcholesterol
1311_19_iodo_ cholesterol
1231_6_iodomethyl_ norcholesterol
123l_12_iodo_ cholesterol
Adrenals
200-203
5.8
1,3
Thyroid
42-61
172-217
0.58
1.5
0.63-0.78
0.09-0.11
0.025
0.0061
Kidneys
1.3-1.6
0.14-0.19
0.034
0,0087
Testes
2,9-3.9
0.59-0.67
0.050
0.024
Spleen
2.0-2.5
0.31-0.34
0.078
0.019
Lungs
0,61-0.77
0.I0-0.12
0,020
0.0051
Liver
Appropriate decay factors for 131I or for 123I were applied to the biological data in Table 1 to yield effective (physical plus biological) clearance data which were used as input to a computer program recently developed for determining internal radiation absorbed dose. t~3. ~4~ The program employs the methodology formulated by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicinetl 5.16) to determine radiation absorbed dose to a target organ from a radionuclide distributed within several source organs. Stored tables of S-factors, the absorbed dose per unit cumulated activity, for selected radionuclides and organs ~16'lv~ are utilized and the total cumulated activity in the various source organs is determined for complete elimination of the radiopharmaceutical by graphic integration of the input effective clearance data. Decisions are made regarding effective uptake of the radiopharmaceutical and the clearance data are extrapolated to infinity assuming either continued effective clearance or physical decay after the last datum point. The tissues listed in Table 1 were used as eight source organs. Blood was considered a source by assuming it uniformly distributed throughout the total body and utilizing total body S-factors. 3. R E S U L T S A N D D I S C U S S I O N The mean absorbed doses for seven target organs are given in Table 2 for the two pharmaceuticals hypothetically labeled with 131I or ~23I. The range of dose estimates for the 13q-labeled compounds represents the two alternatives in extrapolating to infinity for the determination of total cumulated activity; assuming either only physical decay of ~3~I after the last datum point (the higher dose estimate) or continued effective (physical plus biological) clearance as measured at the last datum point (the lower dose estimate). No such ranges appear for the ~23I-labeled compounds since, due to its short physical half-life, both methods of extrapolation to infinity give the same result. The 13q-labeled compounds result in much higher doses (by factors of 15-150) than their equivalent lZ3I-labeled compounds due to the unfavorable
0.070
characteristics of 1311 (beta minus decay and 193 hr half-life) compared with 123I (electron capture decay and 13 hr half-life). As seen by the biological distribution data in Table 1, as much as 60 times (at 3 days after administration) 6-iodomethylnorcholesterol as 19-iodocholesterol accumulates in the rat adrenals. Labeled 19-iodocholesterol, when prepared in >98°; chemical purity according to the method of COUCH and associates, ~1°~ is not taken up sufficiently by the adrenal glands to e'nable their visualization by scintigraphy up to 9 days after intravenous administration,C12~but 6-iodomethylnorcholesterol, when prepared in >98~o chemical purity according to the method of SCOTT and associates ul~ provides satisfactorily high adrenal uptake for imaging from 24 hr up to 7 days after injection. Comparison of the doses in Table 2 from 6-iodomethylnorcholesterol and 19-iodocholesterol with the same radionuclide tag indicate a much higher adrenal dose per mCi (by a factor of 20-35) from the former due to its much more preferential localisation in the adrenals (see Table 1) and a much higher thyroid dose (by a factor of 3) from the latter. Comparison of the radiation absorbed dose estimates presented in this report with earlier published dose estimates reflects the differences in chemical purity, and hence tissue distribution, of the pharmaceuticals. Previous radiation absorbed dose estimates for 311-19-iodocholesterol ~1s-.2o~ utilize biological distribution data from dogs and humans of 1311-19-iodocholesterol prepared by the method of COUNSELL et al/1~ and subsequently shown to contain the isomer. 6-iodomethylnorcholesterol as an impurity in amounts ranging from 10-60')~/° 9.~z~ As Table 1 indicates, "'pure" 19-iodocholesterol has very low adrenal uptake (0.09~o of injected dose at day 1) compared with that of the impure compound (0.4'~"o adrenal uptake of administered activity)/2°~ The resulting adrenal dose for the impure ~311-19-iodocholesterol, 30rad/mCi, ~2°~ is therefore greater than that for "pure" 1311-19-iodocholesterol, 5.8rad/mCi (Table 2). Reported radiation absorbed dose estimates for 311_6.iodomethylnorcholesterol12~ utilize biological
Radiation dosimetry of adrenal imaging agents
distribution data from rats, dogs and humans of 1311.6.iodomethylnorcholesterol prepared by the method of BASMADJIAN et al. 17~ and subsequently shown to be 75-90% pure. t12~ Radiation dose estimates for l 3 ll-6-iodomethylnorcholesterol were reported as 140 rads/mCi to the adrenals and 160 rad/ mCi to the thyroid t21~ from tissue distribution data in rats, where 2.0 and 6.5~o of the administered dose were present in rat adrenals and thyroid respectively at day 1, and 1,7 and 2.1°,~,, respectively, at day 5. tzl) Table 1 shows 1.6 and 0.9% uptake at day 1 in rat adrenals and thyroid respectively, 2.6~'0 adrenal uptake at 3-7 days, and radiation absorbed dose estimates (Table 2) of about 200 and 50rad/mCi to adrenals and thyroid, respectively. The higher adrenal dose estimate for 13q-6-iodomethylnorcholesterol prepared by the method of SCOTT et al. t~x~ reflects its higher and more prolonged adrenal uptake. Thyroid uptake is correspondignly less, and the radiation dose, preferably, lower. The limitations and assumptions of radiation absorbed dose estimates using animal tissue distribution data are obvious. However, the current interest in the preparation of an adrenal imaging agent of high purity 122~warrants the use of the limited existing animal data 112~ for the dose estimates presented here, until human distribution data are available. Additionally, comparison with the radiation dose estimates for the other methods of preparation of 19-iodocholesterol and 6-iodomethylnorcholesteropl8 21) are facilitated since there too animal distribution data were employed. The following additional observations can be made from the results in Table 2 and consideration of the physical properties of 123I and 131I. The frequencies of occurrence of the useful 159 and 364 keV gamma rays from lZ3I and 131I are almost identical, 0.835 and 0.833 per disintegration, respectivelyJ 23~ For the same radiation dose to the adrenal glands, the ~z3I-compound can be administered approximately 150 times more active than the same compound labeled with 13tI, in which case, at 24 or 48 hr after administration the number of useful photons from the ~23I-labeled compound will still be 45 or 14 times, respectively, that from the 13q-labeled compound. For the same radiation dose to the adrenals, the photon flux will be higher, and therefore image quality better, for the x23I-compound rather than the same compound labeled with lalI, up to 100hr after administration. Alternatively, for the same number of useful gamma rays at 24 or 48 hr after administration, 3 or l l times, respectively, more of the shorter-lived 123I-labeled compound would have to be administered than the long-lived ~31I-eompound. However. the radiation dose to the adrenals from the 123I-compound would still be only 0.02 or 0.07 that from the 13q-compound. Finally, the lower energy gamma rays from 12aI are easier to collimate than the high energy gamma
279
rays from 131I and existing commonly-used collimators for 99mTc (140keV gamma rays) can be employed, In conclusion, consideration of the biological distribution, dosimetry, and physical data of 6-iodomethylnorcholesterol and 19-iodocholesterol tagged with 123l or 131I indicates that ~23I-6-iodomethylnorcholesterol prepared in >98°,o purity is preferred for adrenal imaging. Acknowledgements--Thanks are due to MARGARET W. COUCH for supplying the rat distribution data for the ~ZSl-labeled compounds, and to LAWRENCET. FITZGERALD for assistance in running the computer programs.
REFERENCES 1. COUNSELL R. E., RANADE V. V., BLAIR R. J., BEIERWALTES W. H. and WEINHOLD P. A. Steroids 16, 317
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