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

摘要

¹⁸F-Fallypride and ¹¹C-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D2/D3 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 ¹⁸F-fallypride and ¹¹C-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K1, k2, fNDkon, Bmax, and koff 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 (K1/k2) that is three times higher than ¹⁸F-fallypride, primarily due to a slower k2 (FAL:FLB; k2=0.54 min⁻¹:0.18 min⁻¹). The dissociation rate constant, koff, was slower for ¹¹C-FLB457, resulting in a lower KDapp than ¹⁸F-fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D2/D3 binding could be detected in the cerebellum for ¹¹C-FLB457 but not ¹⁸F-fallypride. Both radioligands can be used to image extrastriatal D₂/D₃ receptors, with ¹¹C-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and ¹⁸F-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D₂/D₃ binding in the cerebellum, reference region analysis methods will give a greater bias in BP_ND with ¹¹C-FLB457 than with ¹⁸F-fallypride.