Breast carcinoma cell uptake and Biodistribution of Technetium99m-Carboxymethyl Benzylamide Dextran

Carboxymethyl Benzylamide Dextran (CMDB7) displayed an in vitro inhibitory activity on breast tumor cells. CMDB7 is able to disrupt the interaction of angiogenic growth factors (FGF2, TGF beta and PDGF) with their membrane re ceptors. This compound blocks the angiogenesis of MDA-MB435 carcinoma xenog rafted in mammary fat pad and their lung metastases in nude mice. In this w ork, we studied the uptake of CMDB7 labeled with 99mTc in cultured human br east cancer MCF-7 cell line and the highly tumorigenic MCF-7ras cell line ( Ha-ras-transfected MCF-7 cells) and the in vivo distribution in MCF-7ras tu mor-bearing mice. The Tc-99m-CMDB7 are stable and the intracellular concent ration is time-dependent and reaches a plateau at 180 minutes. Tc-99m CMDB7 uptake is much higher in MCF-7ras cells than MCF-7 cells. Since CMDB7 is i nternalized and could also inhibit cell proliferation by acting at nuclear sites, we investigated the MCF-7ras nuclear localization after cell fractio nation. Cell fractionation revealed a cytoplasmic and nuclear internalizati on of CMDB7. The tumor uptakes of Tc-99m-CMDB7 were 0.34% 0.72% and 0.62% o f the administered doses per gram of tumor tissue at 1 hour, 3 hours and 5 hours respectively after their injection. The blood clearance of Tc-99m CMB D7 was very rapid and the liver, spleen and kidney uptakes of toxicity of C MDB7 in cancer therapy by targeting breast tumors.