Parametric mapping of binding in human brain of D₂ receptor ligands of different affinities

¹¹C-Raclopride has been widely used for PET studies of dopamine D_2/3 receptors in human brain. The long half-life of ¹⁸F may impart advantages to the novel moderate-affinity benzamide ¹⁸F-desmethoxyfallypride and its high-affinity congener ¹⁸F-fallypride for competition studies and for detection of extrastriatal binding. However, the in vivo kinetics of these compounds and the quantification approaches for parametric mapping of their specific bindings have not been systematically compared. Methods: Dynamic emission recordings of the 3 tracers were obtained in groups of healthy subjects. A conventional model, graphical analysis using metabolite-corrected arterial inputs, and models with reference tissue inputs were used to calculate voxelwise parametric maps of the equilibrium distribution volume (V_d) and the binding potential (BP) of the 3 radioligands in brain. To test for bias, voxelwise kinetic results were compared with those obtained by volume-of-interest (VOI) analysis. Results: The V_d and BP estimates obtained by VOI analysis did not differ from the mean of voxelwise estimates in the same striatal volumes. In striatum, the mean ¹⁸F-desmethoxyfallypride BP ranged from 1.9 to 2.5, whereas the mean ¹¹C-raclopride BP ranged from 3 to 4, depending on the method used for calculation. In contrast, the mean BP of ¹⁸F-fallypride ranged from 16 to 27 in striatum and could also be readily quantified in the thalamus. Conclusion: Reference tissue methods for the voxelwise calculation of binding parameters are suitable for parametric mapping of the 3 dopamine D_2/3 receptor ligands.