Characterization of iodovinylmisonidazole as a marker for myocardial hypoxia

Abstract

Misonidazole and related compounds are metabolically trapped in viable cells as a function of reduced cellular pO2. [18F]fluoromisonidazole has been used to detect hypoxia in the heart and in tumors noninvasively with positron emission tomography. The purpose of this study was to characterize the uptake of the iodinated misonidazole congener iodovinylmisonidazole (IVM) in ischemic myocardium. In six open chest dogs (Group 1), the left anterior descending (LAD) coronary artery was partially occluded and in four dogs (Group 2), demand ischemia was produced by the combination of atrial pacing and catecholamine infusion in the presence of a LAD stenosis. [131I]IVM (5-15 microCi/kg, i.v.) was given following the onset of ischemia. Tracer deposition was measured by postmortem tissue sampling 4 hr postinjection and compared to microsphere myocardial blood flow (MBF) measurements made at baseline and at 2 hr postinjection. In Group 1, regional IVM deposition in heart samples within the ischemic area was inversely related to MBF with maximum tissue:blood ratios of 3.2. For a given level of reduced blood flow, IVM uptake was higher in the subendocardium indicating a greater vulnerability of the subendocardium to reductions in oxygen delivery. In Group 2, enhanced IVM deposition was detected as a result of demand ischemia, even in some regions where absolute flow was normal or increased from baseline, indicating that flow per se is not the principal determinant of tracer uptake. We conclude that IVM is a promising marker for myocardial hypoxia with potential clinical application using gamma camera imaging.