Rest/Stress Myocardial Perfusion Imaging by Positron Emission Tomography with 18F-Flurpiridaz: A Feasibility Study in Mice

Background Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18 F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18 F-flurpiridaz is feasible in mice. Methods Rest/stress PET-MPI was performed with 18 F-flurpiridaz (0.6-3.0 MBq) in 29 mice aged 7-8 months. Regadenoson (0.1 μg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18 F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. Results Tracer kinetics were best described by a two-tissue compartment model. K 1 ranged from 6.7-20.0 mL/cm 3 /min, while myocardial volumes of distribution ( V T ) were between 34.6 and 83.6 mL/cm 3 . Of note, myocardial 18 F-flurpiridaz uptake (%ID/g) was significantly correlated with K 1 at rest and following pharmacological stress testing for all time intervals assessed. However, while Spearman’s coefficients (r s ) ranged between 0.478 and 0.672, R 2 values were generally low. In contrast, an excellent correlation of myocardial 18 F-flurpiridaz uptake with V T was obtained, particularly when employing the averaged myocardial uptake from 20-40 min post tracer injection (R 2 ≥0.98). Notably, K 1 and V T were similarly sensitive to pharmacological stress induction. Further, mean stress-to-rest ratios of K 1 , V T , and %ID/g 18 F-flurpiridaz were virtually identical, suggesting that %ID/g 18 F-flurpiridaz can be used to estimate CFR in mice. Conclusion Our findings suggest that a simplified assessment of relative myocardial perfusion and coronary flow reserve (CFR), based on image-derived tracer uptake, is feasible with 18 F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.