CASE REPORT Annals of Nuclear Medicine Vol. 10, No.3, 347-349, 1996 Accumulation of Tc-99m HMDP in hepatic metastasis from colon carcinoma without detectable calcification Susumu SHIOMI,*Tetsuo KUROKI,*Itaru HASEGAWA,* Hiroshi NISHIO,** Kiyohiro AZUMA*** and Hironobu OCHI*** *Third Department of Internal Medicine, **Department of Radiology and ***Division of Nuclear Medicine, Osaka City University Medical School A 51-year-old man was found to have hepatic metastasis from colon carcinoma. Bone scintigraphy with 99mTc-hydroxymethylene diphosphonate showed a ringlike accumulation corresponding to the hepatic mass, which was without calcification on computed tomography. Treatment with chemotherapeutic agents was started. After 4 months, computed tomography showed that the mass was smaller than before and that the margin was calcified. The extraosseous accumulation of the radionuclide may be evidence supporting earlier speculation on calcification that could not yet be detected by computed tomography. Key words: bone scanning, technetium-99m-HMDP, liver accumulation, metastatic tumor, extraosseous accumulation INTRODUCTION ACCUMULATION Of bone-seeking radiopharmaceuticals in the liver, abdominal wall, or ribs1 or in metastases to the liver from colon,2-7 breast,8 or lung9 cancer has been described. The extraosseous accumulation of phosphate compounds is sometimes found without calcification, being detected by radiological or histological inspection. In such patients, radiological calcification may occur later 10 but there have been no longitudinal studies demonstrating abnormal radionuclide accumulation before radiological calcification was detected in an individual subject. Here we report a patient in whom a ringlike accumulation of 99mTc-hydroxymethylene diphosphonate (HMDP) was detected in a hepatic metastasis from colon carcinoma before calcification could be detected by computed tomography. After treatment with chemotherapeutic agents, the metastasis was smaller than before, and calcification could be detected radiologically. CASE REPORT A 51-year-old man came to our hospital with general fatigue and right hypochondralgia one year after surgery for colon carcinoma. On admission, the patient was of moderate build and well-nourished. The liver was palpable on the right midclavicular line 5 cm below the costal margin, but ascites was absent. Laboratory tests showed a white blood cell count of 5,800/mm3, red blood cell count of 399 x 10^4/mm3, total bilirubin of 0.5 mg/dl, aspartate aminotransferase activity of 31 IU/L, alkaline phosphatase activity of 538 IU/L, serum albumin of 4.1 g/dl, lactate dehydrogenase activity of 1,596 WU/L, serum Ca of 4.2 mEq/L, serum P of 2.6 mEq/L, a-fetoprotein of 15 ng/ml, and carcinoembryonic antigen of 838 ng/ml. Enhanced computed tomography (CT) showed a large heterogeneous solid mass of low density with an irregular border, mostly in the right lobe of the liver, but calcification was absent (Fig. 1). Whole body bone scintigraphy was started 3 hr after an injection of 680 MBq of 99mTc-HMDP and gave no evidence of bone metastasis, but it showed increased tracer uptake in a ring shape in the right upper quadrant of the abdomen corresponding to the mass seen on the CT scan. Treatment with injections of 5-fluorouracil and cisplatin was started. After 4 months, carcinoembryonic antigen had decreased to 200 ng/ml. Abdominal CT showed that the mass was smaller than before, with scattered areas of calcification in the area peripheral to the mass; the CT number of the areas was 170 to 300 (that of the aorta was about 100; Fig.2). Bone scintigraphy with 99mTc-HMDP demonstrated a ringlike pattern of radioactivity corresponding to the calcification seen on the CT scan. After 8 months, abdominal CT showed that the mass was smaller than before, with areas of calcification at the periphery (Fig. 3). Bone scintigraphy with 99mTc-HMDP gave the same findings about calcification as the preceding CT scan. The patient died of metastases to the lungs. DISCUSSION In 12 of 22 patients with hepatic metastases from colon carcinoma, Shih et al.6 found extraosseous uptake of 99mTc-HMDP by the metastases; in two patients, the pattern of uptake was ringlike. The radioactivity of the ring was at least as high as that of the ribs, suggesting that calcification was continuing in the periphery of the tumor. Some hepatomas had central necrosis that could be identified when the central area was seen not to be perfused during imaging done with radioindium;11 this necrotic area, where a blood supply was lacking, had a ringlike appearance. The ring or "doughnut" sign seen in cerebral tumors presumably is caused by the same mechanism.12 A ringlike pattern of tracer uptake in hepatic metastases from colon cancers may also be explained by insufficient blood supply if the mass is large. The mechanism of extraosseous uptake of bone-seeking radiopharmaceuticals in tumors other than bone tumors may involve the increased amount of calcium bound to the cell membranes in some tumors,13 or the greater uptake of proteins from the plasma by some tumors than by normal tissue,14 but we do not know details of the mechanism of noncalcified tissue uptake of 99mTc phosphate compounds. The tumor uptake is not an artifact of free pertechnetate because the stomach, where pertechnetate is concentrated, is not imaged.15 Ion exchange between intracellular calcium phosphate and bone-scanning agent incorporating phosphate may also be a mechanism of uptake. 10 Radiological calcification may develop later where bone agents now accumulate, if the subject survives, but there has been no report of calcification being detected after such accumulation in an individual patient. The case presented here is of interest because the abnormal accumulation of radioactivity during bone scintigraphy in the absence of detectable calcification was later followed by calcification seen by abdominal CT. REFERENCES l. Poulose KP, Reba RC, Eckelman WC, Goodyear M. Extra osseous localization of 99mTc-Sn pyrophosphate. Br J Radiol 48: 724-726, 1975. 2. Guiberteau MJ, Potsaid MS. McKusick KA. Accumulation of 99mTc-diphosphonate in four patients with hepatic neoplasm: case reports. J Nucl Med 17: 1060-l061, 1976. 3. Garcia AC, Yeh SDJ, Benua RS. Accumulation of boneseeking radionuclides in liver metastases from colon carcinoma. Clin Nucl Med 2: 265-269, 1977. 4. Romyn AM, Bushnell DL, Freeman ML, Kaplan E. Visualization of metastatic liver disease on technetium-99m bone scintigraphy. Clin Nucl Med 12: 264-267, 1987. 5. Wayslewski A-H, Furst G, Schmitt G. Liver uptake of 99mTc-labeled diphosphonate (DPD) by metastatic lesions from large bowel carcinoma. Eur J Nucl Med 10: 467-468, 1985. 6. Shih W-J, Domstad PA. Lieber A, DeLand FH, Coupal JJ. Localization of 99mTc-HMDP in hepatic metastases from colonic carcinoma. Am J Roentgenol 146: 333-336, 1986. 7. Senda M. Tamaki N, Torizuka K. Fujiwara Y. Kudo M, Tochio H, et al. Accumulation of Tc-99m methylene diphosphonate in calcified metastatic lesions of the liver from colonic carcinoma: comparison with calcification on X-ray computed tomogram. Clin Nucl Med 10: 9-12, 1985. 8. Baumerti JE, Lantieri RL, Horning S, McDougall IR. Liver metastases of breast carcinoma detected on 99mTc-methylene diphosphonate bone scan. Am J Roentgenol 134: 384-391, 1980. 9. Marsh JI, Belzberg ASB, Murphy KC. Uptake of technetium-99m diphosphonate by metastatic large cell carcinoma of the lung. J Nucl Med 29: 726-728, 1988. 10. Lowenthal IS, Tow DE, Chang YC. Accumulation of 99mTc-polyphosphate in two squamous cell carcinomas of the lung: Case report. J Nucl Med 16: 1021-l023, 1975. 11. Yeh S-H, Shih W-J, Liang J-C. Intravenous radionuclide hepatography in the differential diagnosis of intrahepatic mass lesions. J Nucl Med 14: 565-567, 1973. 12. Kim EE. Ring sign in radionuclide cerebral images. Semin Nucl Med 11 : 168-169, 1981. 13. Selkirk JK, Elwood JC, Morris HP. Study on the proposed role of phospholipid in tumor cell membrane. Cancer Res 31 : 27-31, 1971. 14. Ghose T, Nairn RC, Fothergill JE. Uptake of proteins by malignant cells. Nature 196: 1108-1109, 1962. 15. Harper PV, Lathrop KA, Jiminez F, Fink R, Gottschalk A. Technetium 99m as a scanning agent. Radiology 85: 101-l08, 1965.