BMS-747158-02: A novel PET myocardial perfusion imagingagent

Background. BMS-747158-02 is a fluorine 18-labeled pyridaben derivative designed as a new myocardial perfusion imaging agent for use with positron emission tomography (PET). This study evaluated BMS-747158-02. in animal models of cardiac perfusion and compared it with established single photon emission computed tomography agents. Methods and Results. In a rat biodistribution study, BMS-747158-02 (15 mu Ci) had substantially higher myocardial uptake than technetium 99m sestamibi (100 mu Ci) at 15 minutes (3.5% +/- 0.3% %ID/g vs 1.9% +/- 0.1% %ID/g) and 120 minutes (3.2 % +/- 0.4% of injected dose per gram vs 1.8% +/- 0.0% of injected dose per gram) after intravenous administration. Uptake ratios of heart to lung and liver at 60 minutes were also higher for BMS-747158-02 (12.7 +/- 1.4 and 3.7 +/- 0.2, respectively) than Tc-99m sestamilhi (5.9 +/- 0.5 and 2.4 +/- 0.4, respectively). In an isolated rabbit heart model at flow rates of 1.66 to 5.06 mL center dot min(-1)center dot g(-1) wet left ventricular weight, the net BMS-747158-02 heart uptake increased proportionally (0.93 +/- 0.15 to 2.44 +/- 0.40 mL center dot min(-1)center dot g(-1)) and to a greater extent than that of thallium 201 (0.76 +/- 0.02 to 1.11 0.02 mL center dot min(-1)center dot g(-1)) or Tc-99m sestamilhi (0.49 +/- 0.03 to 0.77 +/- 0.08 mL center dot min(-1)center dot g (-1)). PET imaging with BMS-747158-112 showed a clear and sustained cardiac uptake in rats, rabbits, and nonhuman primates with minimal lung interference and rapid liver clearance. Myocardial perfusion deficit zones created by either permanent left coronary ligation or reperfusion after ligation in rats were both clearly identified on PET cardiac images of BMS-747158-02 and had good agreement with in vitro histology. Conclusions. BMS-747158-02 exhibited high and sustained cardiac uptake that was proportional to blood flow, and it represents a new class of PET myocardial perfusion imaging agent. (J Nucl Cardiol 2007;14:189-98).