DELINEATION OF THE BORDER ZONE OF ISCHEMIC RABBIT MYOCARDIUM BY A TECHNETIUM-LABELED NITROIMIDAZOLE

Delineation of viable ischemic myocardium is an important problem in n uclear cardiology. To determine the feasibility of using a technetium- labeled nitroimidazole as an indicator of ischemic myocardium at risk of infarction, me characterized the distribution of a 2-nitroimidazole -derivatized PnAO ligand and its Tc-99m complex, (TcO)-Tc-99m(PnAO)-1- CH2-(2NI) (BMS-181321) in the ischemic territory of the left anterior descending (LAD) coronary artery of the rabbit. In preliminary experim ents, the performance of C-14-deoxyglucose (C-14-2DG) and C-14 misonid azole was assessed relative to apparent regional relative myocardial b lood flow (rMBF) indicated by Tc-99m-teboroxime using double-label aut oradiography in the rabbit LAD occlusion model. After demonstrating th at C-14-2DG and C-14-misonidazole are selectively retained in the late ral border of the ischemic territory, BMS-181321 was co-injected intra venously, with either C-14-2DG or C-14-misonidazole, 20 min after LAD occlusion. In a separate experiment, (TcO)-Tc-99m(pnAO)-6-CH3, a compl ex with the same lipophilicity (log k' 0.26 vs. 0.31) as BMS-181321 bu t which lacks the 2NI moiety, was co-injected with C-14-2DG. After 30 min, the rabbits were sacrificed and C-14/(TC)-T-99m autoradiograms we re obtained from the same tissue sections. The autoradiograms revealed that BMS-181321 was retained with the same microregional distribution as both C-14-2DG and C-14-misonidazole in the border zone of the isch emic LAD territory. The selective retention of BMS-181321 depends on t he presence of the nitroimidazole group, since (TcO)-Tc-99m(PnAO)-6-CH 3 has a uniformly low myocardial distribution in contrast to the enhan ced uptake of co-injected C-14-2DG. These data demonstrate that BMS-18 1321 is selectively retained in hypoxic myocardium and demarcates the ischemic border zone in a manner similar to C-14-2DG and C-14-misonida zole. (C) 1997 Elsevier Science Inc.