Distribution and tumor penetration properties of a radiosensitizer 2-[14C] misonidazole (Ro 07-0582), in mice and rats as studied by whole-body autoradiography.

The hypoxic cell radiosensitizer 2-[14C] misonidazole: 1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol (Ro 07-0582) MISO was administered to mice, control rats, and rats bearing chemically induced rhadbdomyosarcoma. The dose injected was 250 mg/kg and the delivered activity was 100 microCi/kg. Whole-body autoradiography was performed in all animals. We noted the highest uptake of radioactivity in the liver and the kidney. In the liver there was an accumulation of [14C] from 5 min to the 2 hour after treatment, followed by a decrease; this observation is probably related to the metabolic pathway of the drug. The radioactivity was also concentrated in the renal medulla (30 min after injection); this organ is the excretion route for most of the misonidazole or its metabolites. Fecal excretion is also important following biliary elimination. Radioactivity is present in the central nervous system in the first hours after dosage. [14C] Tumor activity was lowest 5 min after IP treatment. By contrast, 12 h after administration of labeled compound the highest activity was detected in this tissue.