Optimizing protocol efficiency in [¹⁸F]flurpiridaz positron emission tomography myocardial perfusion imaging through dose ratio–driven reduction of relative residual activity

Background [¹⁸F]flurpiridaz is a newly FDA-approved tracer for positron emission tomography myocardial perfusion imaging (PET MPI) with a long half-life and improved physical characteristics. However, its long half-life leads to residual rest activity. Prior trials used 30 to 60 minutes delays between rest and stress injections and proposed stress-to-rest dose ratios of 1:2 to 1:3 to mitigate the potential impact of residual rest counts on the stress myocardial perfusion images. Objective To evaluate the effect of stress-to-rest dose ratio and time interval between injections on residual activity. Methods We analyzed consecutive 115 patients who underwent PET MPI with [¹⁸F]flurpiridaz. Relative residual activity was calculated as the ratio of tissue activity concentration (kBq/mL) in the first stress frame to that in the stress tissue phase. Linear regression was used to assess the association of dose ratio and injection time interval with global residual activity. The optimal dose ratio cutoff was identified. Mixed-effects models with interaction terms were used to assess whether the effect varied across vascular territories. Results A total of 115 patients underwent PET MPI. Results showed that increasing the stress-to-rest dose ratio was significantly associated with lower relative residual activity (β = −3.41; 95% confidence interval (CI): −4.72; −2.11 per 1-unit increase), while increasing the time interval between injections up to 39 minutes showed no significant association (β = 0.03 95% CI: −0.12; 0.17 per 1-minute increase) within this time window. The optimal cutoff dose ratio to achieve relative residual activity <20% ranged between 3.2 and 4.3 . Conclusion Increasing the stress-to-rest dose ratio between 3.2 and 4.3 effectively reduces residual activity to <20% of the stress dose across all time intervals, thereby enabling back-to-back imaging and improving protocol efficiency on digital PET systems. Further validation is warranted for older, non-digital scanners.