SMALL AND NEUTRAL (TCO)-O-V BAT, BISAMINOETHANETHIOL (N2S2) COMPLEXESFOR DEVELOPING NEW BRAIN IMAGING AGENTS

Bisaminoethanethiol (BAT) ligands with various gem-dimethyl and amide groups were prepared, and the corresponding neutral Tc-99m complexes w ere prepared and evaluated for their relative stabilities by ligand-ex change reactions, It was demonstrated that technetium complexes contai ning gemdimethyl substituents have higher lipophilicities, whereas tho se with an amide group possess greater stability, which enhances ligan d-exchange reaction. The most interesting observation was that the bra in uptake in rats is not determined only by lipophilicity. Apparently, Tc-99m complexes with an amide functional group display lower brain u ptakes in rats compared to those without an amide group. The brain upt ake was strongly influenced by substituents on the BAT ligand. These f actors are critically important and should be taken into consideration when designing Tc-99m-labeled agents for CNS receptor imaging, (C) 19 98 Elsevier Science Inc.