REFERENCES with 2-(F-18)-fluoro-2 deoxy-D-: correlation with CT. Radiology 1994:190: 1. Kim EE, Chung SK. Tillbury R. et al. Differentiation of residual or recurrent tumors III 116. for post treatment changes with PET using '"F-FDG. Radiographies I992;12(2):269- I 1. Haberkorn U, Strauss LG. Dimitrakopoulou A, et al. PET studies of fluorodeoxy- 279. glucose metabolism in patients with recurrent colorectal tumors receiving radiother 2. Patz F.F Jr. Lowe VJ, Hoffman JM, Paine SS, Hams LK. Goodman PC. Persistent or apy. J NucíMed 1991:32:148 149. recurrent hronchogenic ; Detection with PET and 2-[F-18]-2 deoxy-D- 12. Rozental JM, Levine RL. Nickles RJ, Dobkin JA. Glucose uptake in glioma after treatment: A positron emission tomographic study. Arch Neuroi 1989:46:1302-1307. glucose. Radialo^ 1994;19I:379 382. 13. Martin WH. Delbeke D, Patton JA. et al. FDG-SPECT: correlation with FDG-PET. .V Ichiya Y. Kuwahara Y. Otsuka M. et al. Assessment of response to therapy using fluorine-18- and positron emission tomography. J Nitcl Med JNucI Med 1995:36:988-995. 1991:32:1655 1660. 14. Van Lingen A, Huijgens PC, Visser FC, et al. Performance characteristics of a 4. Bailey JW. Abemayor E. Jabour BA. et al. Positron emission tomography: a new. 511-KeV collimator for imaging positron emission with a standard gamma camera. Eur J NucíMed 1992:19:15-321. precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy. Lan-ngoscope 1992;102:281-288. 15. MacFarlane DJ, Cotton L, Ackermann RJ, et al. Triple-head SPECT with 2-[fluorine- 5. Stollfuss J. dialling G. Friess H, Kocher F. Beger H, Reske SN. 2-[fluorine-18] fluoro 18] fluoro-2-deoxyglucose (FDG): initial evaluation in and comparison with 2-deoxy-D-glucose PET in detection of ; value of quantitative image FDG PET. Radiology 1995:194:425-429. interpretation. Radiology- 1995:195:339 344. 16. Dran WE, Abbott FD, Nicloe MW, Mastin ST, Kuperus JH. Technology for 6. Wahl RL. Cody RL. Hutchins CD. Mudgett EF. Primary and metastatic breast FDG-SPECT with a relatively inexpensive gamma camera—work in progress. Radi carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue ology 1994:191:461-465. FDG. Radiology 1991; 179:765-770. 17. Mertens JD. Bhend WL. Digital coincidence detection: a scanning VLSI implemen 7. Okada J. Yoshikawa K. Imazeki K, et al. Positron emission tomography using tation. Conference Record of the IEEE NSS/MIC. Orlando. FL; 1992:879-881. fluorine-18-fluorodeoxyglucose in malignant lymphoma: a comparison with prolifer- 18. Ziegler SI. Enterrottacher A. Boning G. et al. Performance characteristics of a dual ative activity. J NucíMed 1992:33:325-329. head coincidence camera for the detection of small lesions [Abstract]. J NucíMed 8. Lapela M. Leskinen S, Minn H. et al. Increased glucose metabolism in untreated 1997; 38(suppl):206. non-Hodgkin's lymphoma: a study with positron emission tomography and fluorine- 19. Smith EM, McCroskey Wk, Vickers DS, et al. Simultaneous SPECT and coincidence 18-fluorodeoxyglucose. Blood 1995:9:3522-3527. imaging using a dual detector scintillation camera—works in progress. J NucíMed 9. Rodrigue/ M. Rehn S. Ahlstrom H. Sundstrom C, Glimelius B. Predicting malignancy 1997; 38(suppl):208. grade with PET in non-Hodgkin's lymphoma. J NucíMed 1995:36:1790-1796. 20. Patton JA. Hefetz Y, Shane MD. et al. Measured coincidence imaging parameters of 10. Newman JS. Francis IR. Kaminski MS, Wahl RL. Imaging of lymphoma with PET a clinical dual head scintillation camera. J NucíMed 1997; 38(suppl):221.

Accumulation of -131-Iodocholesterol in Adrenal Métastases

Eriko Tsukamoto, Kazuo Itoh, Kakuko Kanegae, Shinya Kobayashi, Tomohiko Koyanagi and Nagara Tamaki Department of Nuclear Medicine and Urology, Hokkaido University School of Medicine, Sapporo, Japan

coexisting with an have been reported showing Adrenocortical is a useful technique for differentiating increased uptake (concordant uptake) on adrenocortical scintig between types of nonhyperfunctioning adrenal masses. Metastatic raphy (6-8), no cases with concordant uptake have been tumors do not normally accumulate radioiodocholesterol and show discordant uptake on scintigrams. We present two patients who reported in patients with only adrenal metastatic tumors. showed accumulation of 131l-6ß-iodomethyl-19-norcholesterol We have performed adrenocortical scintigraphy on patients (NP59) in the adrenal métastasesfrom renal cell carcinoma. In one with malignant for the evaluation of their adrenal patient with bilateral adrenal métastases,accumulation in the pri tumors, seven of which were histologically proven to have had mary tumor as well as adrenal métastaseswas demonstrated. The adrenal metastatic tumors. Of these patients, five showed adrenal métastasesin both patients were resected and were histo- discordant uptake consistent with cases in previous literature; logically proven to be métastasesfrom clear-cell renal carcinoma. the other two, however, demonstrated accumulation of radio Accumulation of NP59 in metastatic adrenal tumors, although a very iodocholesterol. We present these two cases and discuss the rare finding, suggests a pitfall in the differential diagnosis of adrenal possibility of accumulation of NP59 in the malignant neo cortical tumors. plasms. Key Words: adrenal métastases;adrenocortical scintigraphy;renal cell carcinoma; iodocholesterol CASE REPORTS J NucíMed 1998; 39:656-658 Patient 1 A 58-yr-old woman entered the hospital for resection of a left r\drenocortical scintigraphy is a useful tool for the differential renal cell carcinoma (RCC). CT scan demonstrated a huge right diagnosis of nonhyperfunctioning adrenal masses (1-3). In adrenal mass and the left renal tumor (Fig. 1A). Hormonal patients with malignant neoplasms, it is crucial to distinguish measurements revealed no adrenocortical or medullary dysfunc between metastatic adrenal tumors and other benign tumors to tion. Adrenocortical scintigraphy was performed for the evaluation of the right . She received 37 MBq of '3lI-6 assess tumor staging and plan further management. Accumula tion in the adrenal decreases (discordant uptake) when it ß-iodomethyl-19-norcholesterol (NP59). Posterior and anterior is replaced with neoplasms, because malignant and metastatic abdominal images taken 8 days after injection demonstrated tumors do not accumulate the radiolabeled analog increased uptake (concordant uptake) in the right (4,5). Although several cases of adrenal metastatic tumors compared to the left side (Fig. IB). In addition, diffuse distribution of radioactivity was shown in the vicinity of the left adrenal gland. This radioactivity persisted for 10 days after injection, suggesting Received Jul. 2, 1997; accepted Jul. 3, 1997. radiotracer accumulation in some parts of the primary renal rumor. For correspondence or reprints contact: Eriko Tsukamoto, MD, Department of Nuclear Medicine, Hokkaido University School of Medicine, Kita 15 Nishi 7 Kita-ku The right adrenal gland (7x3 cm, 36 g) was resected and was Sapporo. 060-8638, Japan. histologically proven to be metastatic from the RCC (Fig. 2). No

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FIGURE 1. CT scan (A)demonstrates a left renal tumor (largearrow) and a rightadrenal tumor (smallarrow). A posterior ¡mage8 days after injectionof NP59 (B) shows increased uptake in the right adrenal gland (arrow) and diffuse distribution of radioactivity (arrowhead) under the left adrenal gland. adrenal adenoma tissue coexisted. The left adrenal gland was also evaluation of the adrenal tumor. Only the right adrenal gland was resected along with the left RCC and a small metastatic lesion (5 visualized on the scintigrams (Fig. 3). The findings were inter mm) was found. preted as right with left adrenal suppres sion. The tumor (3x3 cm, 8 g) was resected and was histologi- Patient 2 A right adrenal tumor was found on a CT scan in a 68-yr-old cally demonstrated to be metastatic from the RCC. No metastatic lesions in the left adrenal gland were found visually or in the part man with left RCC. A loss of plasma cortisol circadian rhythm was of the tissue resected with left RCC microscopically. He received observed, although his peripheral concentrations of cortisol and cortisol postoperatively for 1 wk. With 4 days' withdrawal of were normal. He was examined with NP59 for the cortisol, adrenocortical scintigraphy was performed for the re- evaluation of the left adrenal gland. There was no accumulation in the left adrenal gland. A left adrenal tumor, which was progressive and diagnosed as metastasis, developed 6 mo after the operation.

DISCUSSION Two cases demonstrating accumulation of radioiodocholes- terol in the RCC metastatic tumor are presented. In previous articles, no such accumulation in the metastatic tumor has been demonstrated except when those tumors coexisted with adreno cortical adenoma (6-8). Coexistence of adenoma was not demonstrated in these cases. In the first patient, the adrenal mass discovered on CT scan was large and métastaseswere suspected. Increased uptake in the tumor suggested adrenocortical adenoma. The uptake in the right adrenal tumor was prominent but the contralateral adrenal gland was not suppressed. We suspected the coexistence of adenoma and asked the pathologists to re-evaluate the speci mens. Three pathologists from different departments confirmed the diagnosis. They reported that the tissue contained lipids and resembled adrenal tissue. In this patient, diffuse uptake in the

RGURE 2. Metastatic tumor from clear-cell renal carcinoma (arrow). Rich FIGURE 3. Adrenocortical scintigram 8 days after injection.Tracer uptake in lipid content in the cells are noted. Normal adrenocortical cells (arrowhead) the right adrenal gland (arrow) is demonstrated while no accumulation of are in the lower layer. (Hematoxylin and eosin, 100x). tracer in the left adrenal gland is evident.

ACCUMULATIONOF IODINE-!3I-IODOCHOLF.STF.ROL•Tsukamoto et al. 657 vicinity of left adrenal gland was also demonstrated and it was occurs, there may be some connection with the rich cholesterol suspected to be a part of the primary tumor. content of RCC. This finding, although rare, represents one of Scintigraphic findings in the second patient were interpreted the pitfalls of differential diagnosis of adrenal tumors with as concordant uptake because the contralateral adrenal gland adrenocortical scintigraphy using iodocholesterol. was not visualized. However, uptake in the tumor was rather faint. We suspected hypofunction of the contralateral adrenal gland but the patient did well without steroid hormone replace ACKNOWLEDGMENTS ment. Adrenal metastasis in the contralateral side was also We thank Dr. Miyoko Fujita for preparing the photos of the suspected. However, the resected left adrenal gland was normal adrenal specimens. and no macroscopic metastatic lesion was found during the operation. There might be some connection with the left adrenal mass that developed later. However, we could not REFERENCES find a good explanation for nonvisualization of the left 1. Gross MD, Shapiro B, Francis IR, el al. Scintigraphic evaluation of clinically silent adrenal gland. adrenal masses. J NucíMed 1994;35:1145-1152. Accumulation of iodocholesterol was shown only in patients 2. Kobayashi S, Seki T, Nonomura K, Gotoh T, Togashi M, Koyanagi T. Clinical experience of incidentally discovered adrenal tumor with particular reference to with RCC. Clear cells of RCC contain a large quantity of cortical function. J Urol 1993;150:8-I2. cholesterol ester and histologically resemble adrenal . 3. Tsukamoto E, Itoh K, Furudate M. Adrenocortical scintigraphy to evaluate incidental We suggest that this large lipid pool is involved in accumulation adrenal mass (incidemaloma) discovered on computed tomography. Kaku Igaku of NP59. dayman et al. (9) injected RCC patients with NP59 1991:28:629-634. 4. Francis IR, Smid A, Gross MD, et al. Adrenal masses in oncologie patients: functional and measured uptake in various tissues. The highest accumula and morphologic evaluation. Radiologi- 1988;166:353-356. tion of the tracer was shown in the adrenal glands followed by 5. Gross MD, Shapiro B. Buuffard JA, et al. Distinguishing benign from malignant RCC tissue. Tracer activity in RCC was about two times higher euadrenal masses. Ann Inlern Med 1988:109:613-618. than in the kidneys or the liver, although tracer activity in the 6. Hoshi H, Jinnouchi S, Ono S, et al. Scinligraphic demonstration of coexisting adenoma and metastasis of adrenal gland in a patient with bronchogenic carcinoma. Clin Nucí adrenal glands was 10 times higher than that of RCC. In Med 1984;9:717-718. addition, one patient showed faint activity in the area of his 7. Mizuo H, Itoh Y, Takahashi T, Beniko M. Scintigraphic demonstration of lung cancer renal mass on imaging. metastasis to adrenal adenoma: a pitfall in adrenal scintigraphy. Jpn J Clin Riuiiol NP59 binds to low-density lipoproteins (LDL) in the circu 1993:38:633-635. 8. Gross MD, Shapiro B, Francis IR, et al. Scintigraphy of incidentally discovered lation and enters the tissue by LDL receptor-mediated transport bilateral adrenal masses. Em J NucíMed 1995;22:315-321. (10,11). It has been reported that some forms of human solid 9. dayman RV. Figenshau RS. Frigge WF, Forstrom L, Gebhard RL. Transport of circulating serum cholesterol by human renal cell carcinoma. J Ural 1987:137:1262- tumor express an increased amount of LDL receptors (12,13). 1265. Rudling and Collins (14) showed that some RCC expressed 10. Freitas JE. Adrenal cortical and medullary imaging. Semin NucíMed 1995:25:235- higher LDL receptor levels compared to normal tissue 2350. although they were usually low. Although we were not able to 11. Shapiro B, Gross MD. Adrenocortical scintigraphy. In: Murray IPC. Ell PJ, eds. Nuclear medicine in clinical diagnosis and treatment. Edinburgh: Churchill Living measure the level of LDL receptors in our cases, these tumors stone; 1994. may have had an increased number of LDL receptors compared 12. Rudling MJ, Angelin B, Peterson CO, Collins VP, et al. Low density lipoprotein to adrenal glands. An increase in LDL receptors in the tumors receptor activity in human intracranial tumors and its relation to the cholesterol requirement. Cancer Res 1990;50:483-487. is not specific to RCC (12,13), and other tumors have been 13. Rudling MJ. Reihner E, Einarsson K, Ewerth S, Angelin B. Low density lipoprotein reported to have an increase in LDL receptors. receptor-binding activity in human tissues: quantitative importance of hepatic recep tors and evidence for regulation of their expression in vivo. Proc Nail Acad Sci USA 1990:87:3469-3473. CONCLUSION 14. Rudling M, Collins VP. Low density lipoprotein receptor and 3-hydroxy-3-methyl- We report two cases of adrenal metastatic tumors from RCC glutaryl coenzyme a reducíasemRNA levels are coordinately reduced in human renal that accumulated NP59. Although it is not clear why this cell carcinoma. Biuchim Biuphys Ada 1996:1299:75-79.

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