Quantification of cerebral A1 adenosine receptors in humans using [18F]CPFPX and PET: an equilibrium approach

The cerebral A1 adenosine receptor (A1AR) has recently become accessible for in vivo imaging using the selective A1AR ligand [18F]CPFPX and PET. For broad application in neurosciences, imaging at distribution equilibrium is advantageous to quantify stimulus-dependent changes in receptor availability and to avoid arterial blood sampling. Here we propose a bolus/infusion (B/I) protocol to assess the total distribution volume (DVt) of [18F]CPFPX under equilibrium conditions. Employing a bolus-to-infusion ratio of 0.8 h, (near) equilibrium conditions were attained within 60 min. The regional DVt′ given by arterial and venous equilibrium analyses agreed well with conventional two-tissue compartment model analyses (r2 > 0.94 and r2 > 0.84, respectively) and Logan's graphical analyses (r2 = 1.0 and r2 > 0.93, respectively) (n = 4 healthy volunteers). The mean regional DVt′ values of these equilibrium analyses and of venous equilibrium analyses in additional seven volunteers demonstrated excellent agreement with the results of earlier bolus studies (r2 > 0.98). Error simulations show that minor deviations from true equilibrium are associated with negligible to small DVt errors. In conclusion, [18F]CPFPX shows suitable characteristics for A1AR quantification by B/I PET scanning. Carefully standardized venous equilibrium analyses may substitute arterial analyses and thus considerably enhance applicability of A1AR PET in clinical routine.