Martin G V, Cerqueira M D, Caldwell J H, Rasey J S, Embree L, Krohn K A
Division of Cardiology, Seattle Veterans Administration Medical Center, WA 98108.
Circ Res. 1990 Jul;67(1):240-4. doi: 10.1161/01.res.67.1.240.
Fluoromisonidazole is metabolically trapped in viable hypoxic cells in vitro. This property is the basis for the hypothesis that [18F]fluoromisonidazole can be used to detect hypoxic tissues noninvasively using positron emission tomography. To assess the potential usefulness of this compound as a marker for hypoxic myocardium, we measured the accumulation of [3H]fluoromisonidazole in isolated adult rat myocytes under normoxic, hypoxic (5,000 ppm O2), and anoxic conditions. Both anoxia and hypoxia caused a marked increase in [3H]fluoromisonidazole accumulation. Relative to uptake during normoxia, uptake during anoxia was increased by 8.4-fold at 60 minutes and 26.5-fold at 180 minutes (p less than 0.001). During hypoxia, uptake was increased by 4.4-fold at 60 minutes and by 15.3-fold at 180 minutes (p less than 0.0001) and occurred in the absence of significant cell injury as measured by release of creatine kinase and changes in cell morphology. Additional studies demonstrated a slow oxygen-insensitive efflux of fluoromisonidazole or labeled metabolite(s) from myocytes reincubated in drug-free medium. We conclude that fluoromisonidazole is avidly retained in hypoxic myocytes and thus may be suitable for noninvasive detection of hypoxic myocardium using positron emission tomography.
氟米索硝唑在体外可被代谢捕获于存活的缺氧细胞中。这一特性是下述假说的基础，即[18F]氟米索硝唑可用于通过正电子发射断层扫描无创检测缺氧组织。为评估该化合物作为缺氧心肌标志物的潜在实用性，我们在常氧、缺氧（5000 ppm O2）和无氧条件下，测量了[3H]氟米索硝唑在分离的成年大鼠心肌细胞中的蓄积情况。缺氧和无氧均导致[3H]氟米索硝唑蓄积显著增加。与常氧时的摄取相比，无氧时60分钟摄取增加了8.4倍，180分钟时增加了26.5倍（p<0.001）。在缺氧时，60分钟摄取增加了4.4倍，180分钟时增加了15.3倍（p<0.0001），且在通过肌酸激酶释放和细胞形态变化测量未出现明显细胞损伤的情况下发生。进一步研究表明，在无药物培养基中再孵育的心肌细胞中，氟米索硝唑或标记代谢物的氧不敏感外排缓慢。我们得出结论，氟米索硝唑可被缺氧心肌细胞大量保留，因此可能适用于通过正电子发射断层扫描无创检测缺氧心肌。
