bms-747158-02 and Myocardial-Infarction

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.. 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.. Cardiac imaging with BMS747158 allows clear detection of chronic MI without producing any cardiovascular alterations in cardiac compromised rabbits.

Topics: Animals; Chronic Disease; Contrast Media; Myocardial Infarction; Myocardial Perfusion Imaging; Positron-Emission Tomography; Pyridazines; Rabbits; Radiopharmaceuticals

The goal of this study was to evaluate a new (18)F-labeled positron-emission tomography (PET) perfusion tracer, (18)F BMS747158-02, for the assessment of myocardial infarct (MI) size.. Wistar rats were studied 24 hours after ligation of the left coronary artery either permanently (n=15) or transiently (n=16) for 30 minutes. Seven nonoperated rats were studied as controls. The rats were injected with 37 MBq of (18)F BMS747158-02 and imaged with a small animal PET scanner for 20 minutes. Polar maps were generated for measurement of PET defect size, and left ventricular systolic and diastolic volumes were assessed in gated images. As a reference, MI size was determined by 2,3,5-triphenyltetrazolium chloride staining of left ventricular tissue samples. Permanent or transient ligation of the left coronary artery produced transmural or subendocardial MI of variable sizes, respectively. In normal rats, PET imaging demonstrated intense and homogeneous uptake of (18)F BMS747158-02 throughout the myocardium. After ligation, sharply defined perfusion defects were present. Throughout the imaging period, the defect size correlated closely with the MI size either after permanent (r=0.88; P<0.01; mean difference, 1.86%) or transient (r=0.92; P<0.01; mean difference, 2.16%) ligation of the left coronary artery. Moreover, reduction of left ventricular systolic function measured with PET correlated with the MI size (r=-0.81; P<0.01; n=23).. Myocardial (18)F BMS747158-02 PET imaging provides excellent image quality and uptake properties, enabling accurate evaluation of MI size and left ventricular function in rats. It is a promising technique for evaluation of MI size in clinical trials.

Topics: Animals; Fluorine Radioisotopes; Heart; Image Processing, Computer-Assisted; Male; Myocardial Infarction; Myocardial Perfusion Imaging; Myocardium; Positron-Emission Tomography; Pyridazines; Radiopharmaceuticals; Rats; Rats, Wistar