Cardiac imaging and safety evaluation of BMS747158, a novel PET myocardial perfusion imaging agent, in chronic myocardial compromised rabbits

Background BMS747158 labeled with 18 F is being developed for PET myocardial perfusion imaging. Imaging studies showed clear detection of necrotic tissue in acute myocardial infarcted (MI) animals and a good safety profile in normal animals. This study evaluated BMS747158 imaging and cardiovascular safety in a rabbit model of chronic MI with cardiac compromise. Methods and Results Chronic MI rabbits were developed by the left coronary artery ligation followed by 4 weeks recovery. Cardiac PET imaging with BMS747158 (~1.5 mCi, iv) in control rabbits showed clear and uniform myocardial uptake. However, imaging in chronic MI rabbits demonstrated obvious defect area in the left ventricular wall. Before BMS747158 injection, baseline electrocardiogram (ECG) waveforms in lead II configuration were normal with positive QRS complexes in control rabbits. In contrast, MI rabbits exhibited negative QRS complexes with enlarged Q waves and inverted T waves. Baseline values of mean intra-arterial pressure (AP, 61 ± 6 vs 89 ± 11 mmHg), systolic AP (79 ± 11 vs 114 ± 11 mmHg) and diastolic AP (53 ± 4 vs 76 ± 10 mmHg) were lower in MI than in control rabbits. Heart rate (162 ± 36 vs 159 ± 8 beat/minute) and QTc interval (corrected by Fridericia method, 288 ± 17 vs 319 ± 17 ms) were comparable. BMS747158 administration induced no changes from baseline in any of the measured cardiovascular parameters and ECG waveforms in either control or MI rabbits. Conclusions Cardiac imaging with BMS747158 allows clear detection of chronic MI without producing any cardiovascular alterations in cardiac compromised rabbits.