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

Abstract

Background: Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-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 18F-flurpiridaz is feasible in mice. Methods: Rest/stress PET-MPI was performed with 18F-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 18F-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. K1 ranged from 6.7-20.0 mL/cm3/min, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL/cm3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological stress testing for all time intervals assessed. However, while Spearman coefficients (rs) ranged between 0.478 and 0.672, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20-40 min post tracer injection (R2 ≥0.98). Notably, K1 and VT were similarly sensitive to pharmacological stress induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-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 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

Role of sex hormones in modulating myocardial perfusion and coronary flow reserve

“…A volume of interest (VOI) delineating the myocardium was drawn manually by PMOD v.3.8 (PMOD Technologies, Switzerland). Average myocardial [ 18 F]flurpiridaz uptake from 20 to 40 min post injection, calculated from % injected dose per mL of the myocardium (% ID/mL), was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported [9]. Apparent coronary flow reserve (CFR App ) was calculated as the ratio between myocardial [ 18 F]flurpiridaz uptake following vasodilator stress and at resting conditions.…”

“…Apparent coronary flow reserve (CFR App ) was calculated as the ratio between myocardial [ 18 F]flurpiridaz uptake following vasodilator stress and at resting conditions. The term "apparent" is used because CFR App values were calculated without an arterial input function [9].…”

Novel nuclear medical procedures in the detection of microvascular dysfunction

“…46,47 Novel promising tracers, such as 18 F-Flurpiridaz, may facilitate cardiac PET studies, since it has high image contrast in the myocardium, prolonged retention, superior extraction, relatively long half-life, which allows treadmill exercise regimen, so cardiac PET imaging could be performed without cyclotron on site. [20][21][22] Estimation of the absolute blood flow with 18 F-Flurpiridaz can be done by using simplified analysis of retention and SUV, due to superior imaging characteristics with promising results of improved quantitative accuracy, with techniques, which enable eliminating cardiac and patient motion and high diagnostic accuracy. 20,21 New multicentric studies should evaluate new therapy approaches in MVD and therapy evaluation with PET/CT.…”

“…[20][21][22] Estimation of the absolute blood flow with 18 F-Flurpiridaz can be done by using simplified analysis of retention and SUV, due to superior imaging characteristics with promising results of improved quantitative accuracy, with techniques, which enable eliminating cardiac and patient motion and high diagnostic accuracy. 20,21 New multicentric studies should evaluate new therapy approaches in MVD and therapy evaluation with PET/CT. Recent studies have showed that symptomatic patients with MVD and no coronary artery disease can have benefit from ranolazine since PET/CT CFR shows improvement after 30 days.…”

“…This mainly means that their use requires a baby cyclotron in the institution (hospital) itself, considering their short physical half-lives. It seems that new radiopharmaceuticals ( 18 F-Flurpiridaz is in the Phase III clinical trial) will be able to alleviate these shortcomings 20,21.…”