Abstract
[(11)C]-(+)-PHNO is a new dopamine D(2/3) receptor agonist radiotracer which has been successfully used to measure D(2/3) receptor availability in experimental animals and man. Here we report in vivo evaluation in the rat of the biodistribution, metabolism, specificity, selectivity, and dopamine sensitivity of carbon11-labeled PHNO ([(11)C]-3-PHNO) produced by an alternative radiochemical synthesis method. [(11)C]-3-PHNO showed rapid metabolism and clearance from most peripheral organs and tissues. [(11)C]-3-PHNO, but not its polar metabolite, readily crossed the blood-brain barrier and showed high levels of uptake in the D(2/3)-rich striatum. Pretreatment with unlabeled PHNO and the D(2/3) receptor antagonist raclopride indicated that binding in the striatum was specific and selective to D(2/3) receptors. PET studies in anesthetized rats revealed significant reductions in [(11)C]-3-PHNO binding in the striatum following amphetamine administration, indicating sensitivity to increases in endogenous dopamine concentrations. D(2/3) antagonist pretreatment additionally indicated moderate levels of [(11)C]-3-PHNO specific binding in several extrastriatal brain areas-most notably the olfactory bulbs and tubercles, thalamus, and hypothalamus. Of particular interest, approximately 30% of [(11)C]-3-PHNO signal in the cerebellum-a region often used as a "low-binding" reference region for PET quantification-was attributable to specific signal. These data demonstrate that [(11)C]-3-PHNO shows similar tracer characteristics to [(11)C]-(+)-PHNO, but additionally indicate that radiolabeled PHNO may be used to estimate D(2/3) receptor availability in select extrastriatal brain regions with PET.