Comparison of three PET dopamine D2-like receptor ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, in rats

We studied the tracer kinetics of three dopamine D-2-like receptor ligands, [C-11]raclopride ([C-11]RAC), [C-11]nemonapride ([C-11]NEM) and [C-11]N-methylspiperone ([C-11]MSP), in anesthetized rats by tissue dissection, ex vivo ARG and PET in order to clarify their characteristics for PET imaging. The in vivo affinity of the three ligands for the striatum ([C-11]MSP > [C-11]NEM > [C-11]RAC) obeyed the in vitro affinity for dopamine D-2 receptors. The affinity of [C-11]RAC and [C-11]MSP for the cerebellum was very low, but the affinity of [C-11]NEM for the cerebellum was compatible to that for the cortex and was not to be ignored. Also the affinity of [C-11]MSP for the cortex was relatively high. [C-11]RAC showed the highest selectivity. The striatal PET image with [C-11]RAC was clearer than that with [C-11]NEM or [C-11]MSP, but the activity decreased much faster than that measured by tissue dissection because of the partial volume effect. The striatal activity with [C-11]NEM remained high and that with [C-11]MSP gradually increased. [C-11]RAC and [C-11]MSP, but not [C-11]NEM, showed a high accumulation in the periorbital region.