A1 adenosine receptor PET using [18F]CPFPX: displacement studies in humans

Imaging of cerebral A(1) adenosine receptors (A(1)AR) with positron emission tomography (PET) has recently become available for neurological research. To date, it has still not been unraveled if there is a valid reference region without specific radioligand binding that may be used to improve image quantification. We conducted in vivo displacement studies in humans to elucidate this important question using the A(1)AR ligand [(18)F]CPFPX.

Five healthy male volunteers underwent [(18)F]CPFPX bolus/infusion PET with short infusion of unlabelled CPFPX as competitor (n = 4; 0.9 to 4.0 mg) or vehicle (n = 1; control condition) after equilibrium of [(18)F]CPFPX distribution was attained.

Infusion of CPFPX induced a rapid displacement of [(18)F]CPFPX binding in all regions, including the cerebellum (region with lowest binding). Even at the highest competitor dose, no full displacement was reached. Displacement was dose-dependent in all regions except the cerebellum where floor effects and/or noise might have obscured dose dependency. Specific binding was estimated to account for about one third and two thirds of total equilibrium uptake in cerebellum and cortex, respectively.

Although the cerebellum is the region with lowest in vivo [(18)F]CPFPX binding, it is not an ideal reference region devoid of specific binding. Nevertheless, as will be discussed, the use of a reference region analysis may be a useful, non-invasive alternative analysis method in carefully selected applications.