In vivo affinity of [¹⁸F]fallypride for striatal and extrastriatal dopamine D₂ receptors in nonhuman primates

Rationale: [¹⁸F]Fallypride is a new and promising radiotracer, suitable for imaging D₂ receptors with Positron Emission Tomography (PET) in both striatal and extrastriatal regions. The high signal to noise ratio of [¹⁸F]fallypride has been attributed to its high affinity for D₂ receptors (K_D of 0.03 nM, measured in vitro at room temperature). Objectives: We sought to further characterize this tracer in terms of its in vivo affinity, possible affinity differences between brain regions and dependence of in vitro affinity on temperature. Methods: PET scans were performed in baboons over a wide range of concentrations to measure the in vivo K_D of [¹⁸F]fallypride in striatal and extrastriatal regions. Several analytica approaches were used, including nonlinear kinetic modeling and equilibrium methods. Also, in vitro assays were performed at 22 and 37°C. Results: No significant differences in the in vivo K_D were detected between regions. In vivo K_D of [¹⁸F]fallypride was 0.22±0.05 nM in striatum, 0.17±0.05 nM in thalamus, and 0.21±0.07 nM in hippocampus. These values were intermediate between in vitro K_D measured at 22 (0.04±0.03 nM) and 37 degrees (2.03±1.07 nM). Conclusion: The in vivo affinity of [¹⁸F] fallypride was not as high as previously estimated from in vitro values. This property might contribute to the favorable kinetic properties of the tracer. The in vivo affinity was similar between striatal and extrastriatal regions. This result indicates that the measured regional in vivo affinities of this tracer are not affected by putative regional differences in endogenous dopamine, and that [¹⁸F]fallypride is an appropriate tool to provide unbiased estimates of the occupancy of D₂ receptors by antipsychotic drugs in striatal and extrastriatal regions.