SYNTHESIS, CHARACTERIZATION, AND IN-VITRO EVALUATION OF NITROIMIDAZOLE BATO COMPLEXES - NEW TECHNETIUM COMPOUNDS DESIGNED FOR IMAGING HYPOXIC TISSUE

Several technetium-99 BATO (boronic acid adduct of technetium dioximes ) complexes TcX(dioxime)3BR (X = Cl) that contain a boron cap R which bears a 2- or 4-nitroimidazole moiety have been prepared from either T cCI(dioxime)3 or from Tc(dioxime)3(mu-OH)SnCl3 [dioxime = dimethyl gly oxime (DMG) or cyclohexanedione dioxime (CDO)]. Two hydroxy analogs (X = OH) were isolated by treatment of the corresponding chloro complexe s with aqueous NaOH. The complexes have been characterized by elementa l analysis, mass spectrometry, NMR, UV/vis spectroscopy, and high-perf ormance liquid chromatography. These complexes have the potential for selective retention in hypoxic tissue, by a mechanism believed to be t he result of nitro reduction. The electrochemistry and enzymatic reduc tion of these complexes was studied to assess the potential for reduct ion in vivo. The nitroreductase enzyme xanthine oxidase was shown to r educe the nitroimidazole group on the complexes (TcOH(DMG)3BBNO2)-Tc-9 9 and (TcOH(DMG)3BprenNO2)-Tc-99 under anaerobic conditions in the pre sence of hypoxanthine. However, the results indicated that the rate of reduction might be slow in vivo, limiting the suitability of these co mpounds for imaging of regions of hypoxia.