Uptake of cationic technetium complexes in cultured human carcinoma cells and human xenografts

We evaluated lipophilicity, in vitro cell accumulation, and biodistribution of a series of Tc-99m-ether isonitrile complexes to determine whether increased lipophilicity promotes extraction by tumor or enhances imaging properties of the radiopharmaceutical. Nine Tc-99m-sestamibi analogs were synthesized and their lipophilicity was determined. Net cellular accumulation and membrane-potential-independent uptake were quantitatively compared in cultured human colon, breast, and lung carcinoma cells. The biodistribution of [Tc-99m-(2-methoxy-2-ethyl-1-isocyanopropane)(6)](+) (Tc-99m-MMBI) and [Tc-99m-(2-ethoxy-2-methyl-1-isocyanopropane)(6)](+) (Tc-99m-EIBI) was studied in nude mice using subcutaneous, subrenal capsule, and hepatic tumor xenografts. Accumulation of these compounds in colon cells correlated with increasing lipophilicity. Compared with Tc-99m-sestamibi, Tc-99m-EIBI exhibited (i) in colon cells both higher net accumulation and a higher specific/nonspecific uptake ratio; (ii) in all three cell lines higher membrane-potential-dependent accumulation; and (iii) in all subcutaneous tumor xenografts and in colon subrenal capsule and hepatic tumor xenografts higher tumor/background ratios. (C) 1998 Elsevier Science Inc.