High-affinity dopamine D2/D3 PET radioligands 18F-fallypride and 11C-FLB457: A comparison of kinetics in extrastriatal regions using a multiple-injection protocol

F-18-Fallypride and C-11-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D-2/D-3 receptors, but differences in their in vivo kinetics may affect the sensitivity for measuring subtle changes in receptor binding. Focusing on regions of low binding, a direct comparison of the kinetics of F-18-fallypride and C-11-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K-1, k(2), f(ND)k(on), B-max, and k(off) in the midbrain and cortical regions of the rhesus monkey. 11C-FLB457 cleared from the arterial plasma faster and yielded a ND space distribution volume (K-1/k(2)) that is three times higher than 18F-fallypride, primarily due to a slower k(2) (FAL: FLB; k(2) = 0.54 min(-1): 0.18 min(-1)). The dissociation rate constant, koff, was slower for C-11-FLB457, resulting in a lower K-Dapp than F-18-fallypride (FAL: FLB; 0.39 nM: 0.13 nM). Specific D-2/D-3 binding could be detected in the cerebellum for C-11-FLB457 but not F-18-fallypride. Both radioligands can be used to image extrastriatal D-2/D-3 receptors, with C-11-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and F-18-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D-2/D-3 binding in the cerebellum, reference region analysis methods will give a greater bias in BPND with C-11-FLB457 than with F-18-fallypride. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 994-1007; doi: 10.1038/jcbfm.2009.270; published online 30 December 2009