Synthesis and in vitro and in vivo evaluation of three radioiodinated nitroimidazole analogues as tumor hypoxia markers.

Three novel nitroimidazole-based thioflavin-T derivatives, N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl)propanamide, N-[4-(benzothiazol-2-yl) phenyl]-3-(4-nitroimidazole-1-yl)-N-methylpropanamide and N-[4-(benzothiazol-2-yl)phenyl]-3-(2-nitroimidazole-1-yl) propanamide were synthesized and radiolabeled with iodine-131. Three (131)I-labeled compounds continuously accumulated in hypoxic murine sarcoma S180 cells in vitro but not in aerobic cells. Biodistribution results in mice bearing S180 tumor indicated that the tracers could localize in the tumor and eliminate from it slowly. In contrast, the uptake in other organs (stomach excluded) was little and the clearance was quick. The tumor-to-tissue ratios of three compounds all increased with time.