Uptake of 153Sm-DTPA-bis-biotin and 99mTc-DTPA-bis-biotin in rat AS-30D-hepatoma cells

Labeled biotin has been used mainly for pretargeted therapy, an approach for increasing the amount of radioactivity delivered to a cancer cell. The aim of this investigation was to prepare Sm-153-DTPA-bis-biotin and Tc-99m-DTPA-bis-biotin in order to study their in vitro and in vivo uptake in rat AS-30D hepatoma cells found in ascites and in implanted tumor. DTPA-bis-biotin (pH 8) was Sm-153 labeled with (SmCl3)-Sm-153, and Tc-99m-DTPA-bis-biotin was prepared via SnCl, reduction. Radiochemical purity was >98% in both cases. AS-30D hepatoma cells were obtained from ascites of a rat with hepatoma and were propagated in the peritoneum cavity of normal rats. In vitro ascites cell Sm-153-DTPA-bis-biotin uptake was compared with (SmCl3)-Sm-153 cell uptake. The ratio cell Sm-153-DTPA-bis-biotin/(153) SmCl3 was 39.6 and when avidin was added it increased to 50. The ratio Tc-99m-DTPA-bis-biotin/TcO4Na was 8.7. Concentration of Sm-153-DTPA-bis-biotin in tumor 2, 3 and 24 h after administration, was 5, 15 and 3 times higher than in normal muscle (T/nT). Biodistribution in a 0.083-24 h time period showed that Sm-153-DTPA-bis-biotin was taken up only by ascites tumor cells and hepatoma cells. Two and 3 h ratio ascites/liver (As/Lv) was 6.4 and 6.0. For Tc-99m-DTPA-bis-biotin 2 and 3 h T/nT was 15.7 and 4.7 and 2 h As/Lv was 1.4. In conclusion, both radiopharmaceuticals show high uptake in rat AS-30D hepatoma cells in ascites and in implanted tumor. Since lung, thyroid, kidney, liver or pancreas carcinomas are ascites producing cancers 153 Sm-DTPA-bis-biotin would be an adequate therapeutic radiopharmaceutical for these patients whose life quality would be enhanced with control of ascites, and a reduction of the primary tumor and its metastases. (C) 2003 Elsevier Science Inc. All rights reserved.