REFERENCES
1. Kim EE, Chung SK, Tillbury R, et al. Differentiation of residual or recurrent tumors for post treatment changes with PET using 1”F-FDG. Radiographics 1992;12(2):269- 279.
2. Patz EF Jr, Lowe VJ. Hoffman JM, Paine SS, Harris LK, Goodman PC. Persistent or recurrent bronchogenic carcinoma; Detection with PET and 2-[F-18]-2 deoxy-D- glucose. Radiology 1994;191:379-382.
3. Ichiya Y. Kuwabara Y, Otsuka M, et al. Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography. J Nucl Med 1991:32:1655-1660.
4. Bailey JW, Abemayor E. Jabour BA, et al. Positron emission tomography: a new, precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy. Laryngoscope 1992;102:281-288.
5. Stollfuss J, Glatting G, Friess H, Kocher F, Beger H, Reske SN. 2-[fluorine-18] fluoro 2-deoxy-D-glucose PET in detection of pancreatic cancer; value of quantitative image interpretation. Radiology 1995;195:339-344.
6. Wahl RL, Cody RL, Hutchins GD, Mudgett EE. Primary and metastatic breast carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue FDG. Radiology 1991;179:765-770.
7. Okada J, Yoshikawa K, Imazeki K, et al. Positron emission tomography using fluorine-18-fluorodeoxyglucose in malignant lymphoma: a comparison with prolifer- ative activity. J Nucl Med 1992:33:325-329.
8. Lapela M, Leskinen S, Minn H, et al. Increased glucose metabolism in untreated non-Hodgkin’s lymphoma: a study with positron emission tomography and fluorine- 18-fluorodeoxyglucose. Blood 1995;9:3522-3527.
9. Rodriguez M, Rehn S, Ahlstrom H, Sundstrom C, Glimelius B. Predicting malignancy grade with PET in non-Hodgkin’s lymphoma. J Nucl Med 1995;36:1790-1796.
10. Newman JS, Francis IR, Kaminski MS, Wahl RL. Imaging of lymphoma with PET
with 2-(F-18)-fluoro-2 deoxy-D-glucose: correlation with CT. Radiology 1994;190: 111-116.
11. Haberkorn U, Strauss LG, Dimitrakopoulou A, et al. PET studies of fluorodeoxy- glucose metabolism in patients with recurrent colorectal tumors receiving radiother- apy. J Nucl Med 1991;32:148-149.
12. Rozental JM, Levine RL, Nickles RJ, Dobkin JA. Glucose uptake in glioma after treatment: A positron emission tomographic study. Arch Neurol 1989;46:1302-1307.
13. Martin WH, Delbeke D, Patton JA, et al. FDG-SPECT: correlation with FDG-PET. J Nucl Med 1995;36:988-995.
14. Van Lingen A, Huijgens PC, Visser FC, et al. Performance characteristics of a 511-KeV collimator for imaging positron emission with a standard gamma camera. Eur J Nucl Med 1992;19:15-321.
15. MacFarlane DJ, Cotton L, Ackermann RJ, et al. Triple-head SPECT with 2-[fluorine- 18] fluoro-2-deoxyglucose (FDG): initial evaluation in oncology and comparison with FDG PET. Radiology 1995;194:425-429.
16. Dran WE, Abbott FD, Nicloe MW, Mastin ST, Kuperus JH. Technology for FDG-SPECT with a relatively inexpensive gamma camera-work in progress. Radi- ology 1994;191:461-465.
17. Mertens JD, Bhend WL. Digital coincidence detection: a scanning VLSI implemen- tation. Conference Record of the IEEE NSS/MIC. Orlando, FL; 1992:879-881.
18. Ziegler SI, Enterrottacher A, Boning G, et al. Performance characteristics of a dual head coincidence camera for the detection of small lesions [Abstract]. J Nucl Med 1997; 38(suppl):206.
19. Smith EM, McCroskey Wk, Vickers DS, et al. Simultaneous SPECT and coincidence imaging using a dual detector scintillation camera-works in progress. J Nucl Med 1997; 38(suppl):208.
20. Patton JA, Hefetz Y, Shane MD, et al. Measured coincidence imaging parameters of a clinical dual head scintillation camera. J Nucl Med 1997; 38(suppl):221.
Accumulation of Iodine-131-Iodocholesterol in Renal Cell Carcinoma Adrenal Metastases
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
Adrenocortical scintigraphy is a useful technique for differentiating between types of nonhyperfunctioning adrenal masses. Metastatic tumors do not normally accumulate radioiodocholesterol and show discordant uptake on scintigrams. We present two patients who showed accumulation of 1311-68-iodomethyl-19-norcholesterol (NP59) in the adrenal metastases from renal cell carcinoma. In one patient with bilateral adrenal metastases, accumulation in the pri- mary tumor as well as adrenal metastases was demonstrated. The adrenal metastases in both patients were resected and were histo- logically proven to be metastases from clear-cell renal carcinoma. Accumulation of NP59 in metastatic adrenal tumors, although a very rare finding, suggests a pitfall in the differential diagnosis of adrenal cortical tumors.
Key Words: adrenal metastases; adrenocortical scintigraphy; renal cell carcinoma; iodocholesterol
J Nucl Med 1998; 39:656-658
Adrenocortical scintigraphy is a useful tool for the differential diagnosis of nonhyperfunctioning adrenal masses (1-3). In patients with malignant neoplasms, it is crucial to distinguish between metastatic adrenal tumors and other benign tumors to assess tumor staging and plan further management. Accumula- tion in the adrenal gland decreases (discordant uptake) when it is replaced with neoplasms, because malignant and metastatic tumors do not accumulate the radiolabeled cholesterol analog (4,5). Although several cases of adrenal metastatic tumors
coexisting with an adenoma have been reported showing increased uptake (concordant uptake) on adrenocortical scintig- raphy (6-8), no cases with concordant uptake have been reported in patients with only adrenal metastatic tumors.
We have performed adrenocortical scintigraphy on patients with malignant neoplasms for the evaluation of their adrenal tumors, seven of which were histologically proven to have had adrenal metastatic tumors. Of these patients, five showed discordant uptake consistent with cases in previous literature; the other two, however, demonstrated accumulation of radio- iodocholesterol. We present these two cases and discuss the possibility of accumulation of NP59 in the malignant neo- plasms.
CASE REPORTS
Patient 1
A 58-yr-old woman entered the hospital for resection of a left renal cell carcinoma (RCC). CT scan demonstrated a huge right adrenal mass and the left renal tumor (Fig. 1A). Hormonal measurements revealed no adrenocortical or medullary dysfunc- tion. Adrenocortical scintigraphy was performed for the evaluation of the right adrenal tumor. She received 37 MBq of 1311-6 ß-iodomethyl-19-norcholesterol (NP59). Posterior and anterior abdominal images taken 8 days after injection demonstrated increased uptake (concordant uptake) in the right adrenal gland compared to the left side (Fig. 1B). 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 radiotracer accumulation in some parts of the primary renal tumor. The right adrenal gland (7 X 3 cm, 36 g) was resected and was histologically proven to be metastatic from the RCC (Fig. 2). No
A
B
adrenal adenoma tissue coexisted. The left adrenal gland was also resected along with the left RCC and a small metastatic lesion (5 mm) was found.
Patient 2
A right adrenal tumor was found on a CT scan in a 68-yr-old man with left RCC. A loss of plasma cortisol circadian rhythm was observed, although his peripheral concentrations of cortisol and aldosterone were normal. He was examined with NP59 for the
evaluation of the adrenal tumor. Only the right adrenal gland was visualized on the scintigrams (Fig. 3). The findings were inter- preted as right adrenocortical adenoma with left adrenal suppres- sion. The tumor (3 X 3 cm, 8 g) was resected and was histologi- cally demonstrated to be metastatic from the RCC. No metastatic lesions in the left adrenal gland were found visually or in the part of the tissue resected with left RCC microscopically. He received cortisol postoperatively for 1 wk. With 4 days’ withdrawal of 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 metastases were 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
vicinity of left adrenal gland was also demonstrated and it was suspected to be a part of the primary tumor.
Scintigraphic findings in the second patient were interpreted as concordant uptake because the contralateral adrenal gland 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- ment. Adrenal metastasis in the contralateral side was also suspected. However, the resected left adrenal gland was normal 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 find a good explanation for nonvisualization of the left adrenal gland.
Accumulation of iodocholesterol was shown only in patients with RCC. Clear cells of RCC contain a large quantity of cholesterol ester and histologically resemble adrenal glands. We suggest that this large lipid pool is involved in accumulation of NP59. Clayman et al. (9) injected RCC patients with NP59 and measured uptake in various tissues. The highest accumula- tion of the tracer was shown in the adrenal glands followed by RCC tissue. Tracer activity in RCC was about two times higher than in the kidneys or the liver, although tracer activity in the adrenal glands was 10 times higher than that of RCC. In addition, one patient showed faint activity in the area of his renal mass on radionuclide imaging.
NP59 binds to low-density lipoproteins (LDL) in the circu- lation and enters the tissue by LDL receptor-mediated transport (10,11). It has been reported that some forms of human solid tumor express an increased amount of LDL receptors (12,13). Rudling and Collins (14) showed that some RCC expressed higher LDL receptor levels compared to normal kidney tissue although they were usually low. Although we were not able to measure the level of LDL receptors in our cases, these tumors may have had an increased number of LDL receptors compared to adrenal glands. An increase in LDL receptors in the tumors is not specific to RCC (12,13), and other tumors have been reported to have an increase in LDL receptors.
CONCLUSION
We report two cases of adrenal metastatic tumors from RCC that accumulated NP59. Although it is not clear why this
occurs, there may be some connection with the rich cholesterol content of RCC. This finding, although rare, represents one of the pitfalls of differential diagnosis of adrenal tumors with adrenocortical scintigraphy using iodocholesterol.
ACKNOWLEDGMENTS
We thank Dr. Miyoko Fujita for preparing the photos of the adrenal specimens.
REFERENCES
1. Gross MD, Shapiro B, Francis IR, et al. Scintigraphic evaluation of clinically silent adrenal masses. J Nucl Med 1994;35:1145-1152.
2. Kobayashi S, Seki T, Nonomura K, Gotoh T, Togashi M, Koyanagi T. Clinical experience of incidentally discovered adrenal tumor with particular reference to cortical function. J Urol 1993;150:8-12.
3. Tsukamoto E, Itoh K, Furudate M. Adrenocortical scintigraphy to evaluate incidental adrenal mass (incidentaloma) discovered on computed tomography. Kaku Igaku 1991;28:629-634.
4. Francis IR, Smid A, Gross MD, et al. Adrenal masses in oncologic patients: functional and morphologic evaluation. Radiology 1988;166:353-356.
5. Gross MD, Shapiro B, Buuffard JA, et al. Distinguishing benign from malignant euadrenal masses. Ann Intern Med 1988;109:613-618.
6. Hoshi H, Jinnouchi S, Ono S, et al. Scintigraphic demonstration of coexisting adenoma and metastasis of adrenal gland in a patient with bronchogenic carcinoma. Clin Nucl Med 1984;9:717-718.
7. Mizuo H, Itoh Y, Takahashi T, Beniko M. Scintigraphic demonstration of lung cancer metastasis to adrenal adenoma: a pitfall in adrenal scintigraphy. Jpn J Clin Radiol 1993;38:633-635.
8. Gross MD, Shapiro B, Francis IR, et al. Scintigraphy of incidentally discovered bilateral adrenal masses. Eur J Nucl Med 1995;22:315-321.
9. Clayman RV, Figenshau RS, Prigge WF, Forstrom L, Gebhard RL. Transport of circulating serum cholesterol by human renal cell carcinoma. J Urol 1987;137:1262- 1265.
10. Freitas JE. Adrenal cortical and medullary imaging. Semin Nucl Med 1995;25:235- 2350.
11. Shapiro B, Gross MD. Adrenocortical scintigraphy. In: Murray IPC, Ell PJ, eds. Nuclear medicine in clinical diagnosis and treatment. Edinburgh: Churchill Living- stone; 1994.
12. Rudling MJ, Angelin B, Peterson CO, Collins VP, et al. Low density lipoprotein receptor activity in human intracranial tumors and its relation to the cholesterol requirement. Cancer Res 1990;50:483-487.
13. Rudling MJ, Reihner E, Einarsson K, Ewerth S, Angelin B. Low density lipoprotein receptor-binding activity in human tissues: quantitative importance of hepatic recep- tors and evidence for regulation of their expression in vivo. Proc Natl Acad Sci USA 1990;87:3469-3473.
14. Rudling M, Collins VP. Low density lipoprotein receptor and 3-hydroxy-3-methyl- glutaryl coenzyme a reductase mRNA levels are coordinately reduced in human renal cell carcinoma. Biochim Biophys Acta 1996;1299:75-79.