Effects of food intake and anesthetic on cardiac imaging and uptake of BMS747158-02 in comparison with FDG.

BACKGROUND: BMS747158-02 is an (18)F-labeled agent being developed for PET myocardial perfusion imaging. This study examined impacts of feeding state and anesthetic on cardiac imaging and uptake of this agent in rats in comparison with (18)F-fluorodeoxyglucose (FDG). METHODS AND RESULTS: Studies were performed in rats either nonfasted or food deprived for 20 hours and anesthetized with either sodium pentobarbital (Pentob) or ketamine and xylazine (Ket/Xyl). Influences of the feeding state and anesthesia were examined by measurement of blood glucose levels, and tissue biodistribution and cardiac imaging of BMS747158-02 and FDG. The blood glucose levels were lower in fasted than nonfasted rats before anesthesia (91 +/- 11 vs 122 +/- 10 mg/dL) and the levels did not significantly change when anesthetized with Pentob. However, the levels increased markedly by 262 +/- 64 mg/dL in nonfasted rats anesthetized with Ket/Xyl. At 60 minutes post-injection, the heart uptake of FDG was significantly lower in fasted than nonfasted rats (0.2 +/- 0.1 vs 2.8 +/- 1.5%ID/g). However, the heart uptake of BMS747158-02 did not differ under these conditions (3.3 +/- 0.9 vs 3.6 +/- 0.9%ID/g, respectively). In nonfasted rats, the heart uptake of FDG was markedly lower when anesthetized with Ket/Xyl than with Pentobl (0.2 +/- 0.1 vs 2.8 +/- 1.5%ID/g). In contrast, the heart uptake of BMS747158-02 was similar with both anesthetics (3.6 +/- 0.5 vs 3.6 +/- 0.9%ID/g). Consistent with the biodistribution studies, the myocardium was not visible following FDG imaging in fasted rats, but clearly seen with BMS747158-02 in both fasted and nonfasted rats anesthetized with either anesthetic. CONCLUSIONS: Unlike FDG, BMS747158-02 cardiac images are clear and not affected by the feeding state and anesthetics.

BMS-747158-02: a novel PET myocardial perfusion imaging agent.

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 microCi) had substantially higher myocardial uptake than technetium 99m sestamibi (100 microCi) 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 sestamibi (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 x min(-1).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.min(-1) x g(-1)) and to a greater extent than that of thallium 201 (0.76 +/- 0.02 to 1.11 +/- 0.02 mL x min(-1) x g(-1)) or Tc-99m sestamibi (0.49 +/- 0.03 to 0.77 +/- 0.08 mL x min(-1) x g(-1)). PET imaging with BMS-747158-02 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.