Minimally Invasive Quantification Of Cerebral P2x7r Occupancy Using Dynamic [F-18]Jnj-64413739 Pet And Mra-Driven Image Derived Input Function

[F-18]JNJ-64413739 has been evaluated as PET-ligand for in vivo quantification of purinergic receptor subtype 7 receptor (P2X7R) using Logan graphical analysis with a metabolite-corrected arterial plasma input function. In the context of a P2X7R PET dose occupancy study, we evaluated a minimally invasive approach by limiting arterial sampling to baseline conditions. Meanwhile, post dose distribution volumes (V-T) under blocking conditions were estimated by combining baseline blood to plasma ratios and metabolite fractions with an MR angiography driven image derived input function (IDIF). Regional postdose V-T,V-IDIF values were compared with corresponding V-T,V-AIF estimates using a arterial input function (AIF), in terms of absolute values, test-retest reliability and receptor occupancy. Compared to an invasive AIF approach, postdose V-T,V-IDIF values and corresponding receptor occupancies showed only limited bias (Bland-Altman analysis: 0.06 +/- 0.27 and 3.1% +/- 6.4%) while demonstrating a high correlation (Spearman rho = 0.78 and rho = 0.98 respectively). In terms of test-retest reliability, regional intraclass correlation coefficients were 0.98 +/- 0.02 for V-T,V-IDIF compared to 0.97 +/- 0.01 for V-T,V-AIF. These results confirmed that a postdose IDIF, guided by MR angiography and using baseline blood and metabolite data, can be considered for accurate [F-18]JNJ-64413739 PET quantification in a repeated PET study design, thus avoiding multiple invasive arterial sampling and increasing dosing flexibility.