Tissue distribution of 14C- and 3H-labelled misonidazole in the tumor-bearing mouse

The retention of labelled misonidazole (MISO) was measured in a range of normal tissues in the mouse 24 hr after the intravenous injection of [14C]MISO (ring labelled) and [3H]-MISO (side-arm labelled). For [14C]MISO the 24 hr tissue retention, in order of the highest to the lowest levels (excluding pathways of excretion), was esophageal epithelium, liver, foot pad, eyelid, lung, subcutaneous lung tumor (A110), esophageal wall, uterus, eye ball, blood, salivary gland, spleen, voluntary muscle, pancreas, inguinal fat. It was assumed that the 14C represented MISO metabolite(s) bound to macromolecules. An approximately similar pattern was observed for [3H]MISO, but a higher percentage of the injected activity per gram of tissue was retained, probably due to the presence of tritiated water in the tissues. It has generally been assumed that significant levels of MISO binding are restricted to hypoxic tissues, for example tumors, but the present results show that significant levels of binding can also occur in apparently normoxic tissues. The explanation is put forward that this binding may be due to local high levels of nitroreductase capacity.