Binding of the hypoxia tracer [3H]misonidazole in cerebral ischemia.

Abstract

Radiolabelled misonidazole, a radiosensitizing drug that binds to viable hypoxic tumor cells, may be useful in identifying hypoxic cells in cerebrovascular disease. Its potential was investigated in the gerbil stroke model. Biodistribution of [3H]misonidazole was measured in normal gerbils and animals that had been subjected to right common carotid artery ligation to produce cerebral ischemia. The uptake of [3H]misonidazole in the right cerebral hemisphere and right/left hemispheral uptake ratios correlated positively with the severity of the stroke when measured 6-9 hours after carotid ligation. Histologic studies in symptomatic ligated animals showed ipsilateral widespread but patchy acute ischemic changes as well as areas that showed no morphological changes. Microscopic autoradiography in these animals showed diffuse heavy labelling only in the ipsilateral hemisphere. This was over areas that had histological damage as well as in adjacent areas that appeared intact. Studies comparing blood flow measured with [14C]iodoantipyrine and [3H]misonidazole retention in gerbils with carotid artery ligations indicated that flow is not a major determinant of retention of this hypoxia tracer. We conclude that a misonidazole congener labelled with a gamma- or positron-emitting isotope may be useful in nuclear imaging of the degree and regional distribution of hypoxic tissue in cerebrovascular disease.