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

The cerebral A(1) adenosine receptor (A(1)AR) has recently become accessible for in vivo imaging using the selective A(1)AR ligand [(18)F]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 (DV(t)) of [(18)F]CPFPX under equilibrium conditions. Employing a bolus-to-infusion ratio of 0.8 h, (near) equilibrium conditions were attained within 60 min. The regional DV(t)' given by arterial and venous equilibrium analyses agreed well with conventional two-tissue compartment model analyses (r(2) > 0.94 and r(2) > 0.84, respectively) and Logan's graphical analyses (r(2) = 1.0 and r(2) > 0.93, respectively) (n = 4 healthy volunteers). The mean regional DV(t)' values of these equilibrium analyses and of venous equilibrium analyses in additional seven volunteers demonstrated excellent agreement with the results of earlier bolus studies (r(2) > 0.98). Error simulations show that minor deviations from true equilibrium are associated with negligible to small DV(t) errors. In conclusion, [(18)F]CPFPX shows suitable characteristics for A(1)AR quantification by B/I PET scanning. Carefully standardized venous equilibrium analyses may substitute arterial analyses and thus considerably enhance applicability of A(1)AR PET in clinical routine.