Delineation of the border zone of ischemic rabbit myocardium by a technetium-labeled nitroimidazole. Export

@article{citeulike:754983, abstract = {Delineation of viable ischemic myocardium is an important problem in nuclear cardiology. To determine the feasibility of using a technetium-labeled nitroimidazole as an indicator of ischemic myocardium at risk of infarction, we characterized the distribution of a 2-nitroimidazole-derivatized PnAO ligand and its 99mTc complex, 99mTcO(PnAO)-1-CH2-(2NI) (BMS-181321) in the ischemic territory of the left anterior descending (LAD) coronary artery of the rabbit. In preliminary experiments, the performance of 14C-deoxyglucose (14C-2DG) and 14C-misonidazole was assessed relative to apparent regional relative myocardial blood flow (rMBF) indicated by 99mTc-teboroxime using double-label autoradiography in the rabbit LAD occlusion model. After demonstrating that 14C-2DG and 14C-misonidazole are selectively retained in the lateral border of the ischemic territory, BMS-181321 was co-injected intravenously, with either 14C-2DG or 14C-misonidazole, 20 min after LAD occlusion. In a separate experiment, 99mTcO(PnAO)-6-CH3, a complex with the same lipophilicity (log k' 0.26 vs. 0.31) as BMS-181321 but which lacks the 2NI moiety, was co-injected with 14C-2DG. After 30 min, the rabbits were sacrificed and 14C/99mTc autoradiograms were obtained from the same tissue sections. The autoradiograms revealed that BMS-181321 was retained with the same microregional distribution as both 14C-2DG and 14C-misonidazole in the border zone of the ischemic LAD territory. The selective retention of BMS-181321 depends on the presence of the nitroimidazole group, since 99mTcO(PnAO)-6-CH3 has a uniformly low myocardial distribution in contrast to the enhanced uptake of co-injected 14C-2DG. These data demonstrate that BMS-181321 is selectively retained in hypoxic myocardium and demarcates the ischemic border zone in a manner similar to 14C-2DG and 14C-misonidazole.}, address = {Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.}, author = {Di Rocco, R. J. and Bauer, A. A. and Pirro, J. P. and Kuczynski, B. L. and Belnavis, L. and Chan, Y. W. and Linder, K. E. and Narra, R. K. and Nowotnik, D. P. and Nunn, A. D.}, citeulike-article-id = {754983}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/9228654}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=9228654}, issn = {0969-8051}, journal = {Nucl Med Biol}, keywords = {cardiology, infarction, ischemia, nuclear, nuclear\_cardiology, regional\_ischemia, ri2d}, month = {April}, number = {3}, pages = {201--207}, posted-at = {2006-07-12 16:47:09}, priority = {0}, title = {Delineation of the border zone of ischemic rabbit myocardium by a technetium-labeled nitroimidazole.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/9228654}, volume = {24}, year = {1997} }

TY - JOUR ID - citeulike:754983 L3 - citeulike-article-id:754983 N2 - Delineation of viable ischemic myocardium is an important problem in nuclear cardiology. To determine the feasibility of using a technetium-labeled nitroimidazole as an indicator of ischemic myocardium at risk of infarction, we characterized the distribution of a 2-nitroimidazole-derivatized PnAO ligand and its 99mTc complex, 99mTcO(PnAO)-1-CH2-(2NI) (BMS-181321) in the ischemic territory of the left anterior descending (LAD) coronary artery of the rabbit. In preliminary experiments, the performance of 14C-deoxyglucose (14C-2DG) and 14C-misonidazole was assessed relative to apparent regional relative myocardial blood flow (rMBF) indicated by 99mTc-teboroxime using double-label autoradiography in the rabbit LAD occlusion model. After demonstrating that 14C-2DG and 14C-misonidazole are selectively retained in the lateral border of the ischemic territory, BMS-181321 was co-injected intravenously, with either 14C-2DG or 14C-misonidazole, 20 min after LAD occlusion. In a separate experiment, 99mTcO(PnAO)-6-CH3, a complex with the same lipophilicity (log k' 0.26 vs. 0.31) as BMS-181321 but which lacks the 2NI moiety, was co-injected with 14C-2DG. After 30 min, the rabbits were sacrificed and 14C/99mTc autoradiograms were obtained from the same tissue sections. The autoradiograms revealed that BMS-181321 was retained with the same microregional distribution as both 14C-2DG and 14C-misonidazole in the border zone of the ischemic LAD territory. The selective retention of BMS-181321 depends on the presence of the nitroimidazole group, since 99mTcO(PnAO)-6-CH3 has a uniformly low myocardial distribution in contrast to the enhanced uptake of co-injected 14C-2DG. These data demonstrate that BMS-181321 is selectively retained in hypoxic myocardium and demarcates the ischemic border zone in a manner similar to 14C-2DG and 14C-misonidazole. IS - 3 JF - Nucl Med Biol SN - 0969-8051 AD - Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. EP - 207 TI - Delineation of the border zone of ischemic rabbit myocardium by a technetium-labeled nitroimidazole. VL - 24 SP - 201 KW - cardiology KW - infarction KW - ischemia KW - nuclear KW - nuclear_cardiology KW - regional_ischemia KW - ri2d AU - Di Rocco, RJ AU - Bauer, AA AU - Pirro, JP AU - Kuczynski, BL AU - Belnavis, L AU - Chan, YW AU - Linder, KE AU - Narra, RK AU - Nowotnik, DP AU - Nunn, AD PY - 1997/04// UR - http://view.ncbi.nlm.nih.gov/pubmed/9228654 ER -