Rest/stress myocardial perfusion imaging by positron emission tomography with (18)F-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 27 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 to 20.0 mL·cm(−3)·min(−1), 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 vasodilation for all time intervals assessed. However, while Spearman’s coefficients (r(s)) ranged between 0.478 and 0.681, 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 to 40 min post tracer injection (R(2) ≥ 0.98). Notably, K(1) and V(T) were similarly sensitive to pharmacological vasodilation 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 coronary flow reserve (CFR) in mice. CONCLUSION: Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with (18)F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents. SUPPLEMENTARY INFORMATION: The online version of this article contains supplementary material available (10.1007/s12350-022-02968-9).