Kinetics of a putative hypoxic tissue marker, technetium-99m- nitroimidazole (BMS181321), in normoxic, hypoxic, ischemic and stunned myocardium

This study focused on the kinetics of the newly developed ^99mTc- nitroimidazole, propyleneamine oxime-1,2-nitroimidazole (BMS181321) in the different setting of myocardial perfusion states and oxygenation levels, and compared the kinetics of BMS181321 with those of other technetium analogues. Methods: The kinetics of BMS181321 were evaluated in isolated perfused rat hearts. Technetium-99m-hexamethyl propyleneamine oxime (HMPAO) and a non- nitroimidazole-containing analogue of BMS181321 (6-methyl propyleneamine oxime; PAO-6-Me) were used to compare their kinetics with those of BMS181321. Results: BMS181321 cleared quickly from normoxic hearts and the retention in the myocardium 10 min after injection was 0.84% ± 0.04% ID/g wet wt (mean ± s.e.m.). In contrast, BMS181321 was retained after reperfusion when it was injected before ischemia; the uptake in the myocardium 10 min after reperfusion was significantly greater than in controls (23.9% ± 3.9% ID/g wt, p < 0.05). Conclusions: These results indicate that ^99mTc-BMS181321 is well trapped in ischemic myocardium and moderately trapped in hypoxic myocardium, but washed out quickly in stunned myocardium. The residence time influences the amount retained.