Abstract
Several dopamine D(2) agonist radioligands have been used with positron emission tomography (PET), including [(11)C-]-(-)-MNPA, [(11)C-]-(-)-NPA and [(11)C]-(+)-PHNO. These radioligands are considered particularly powerful for detection of endogenous dopamine release, but they either provide PET brain images with limited contrast or have affinity for both D(2) and D(3) receptors. We here present the carbon-11 radiolabeling and ex vivo evaluation of 2-Cl-(-)-NPA, a novel PET-tracer candidate with high in vitro D(2)/D(3) selectivity. 2-Cl-[(11)C]-(-)-NPA and [(11)C]-(-)-NPA were synthesized by a two step N-acylation-reduction process using [(11)C]-propionyl chloride. Awake rats were injected with either tracer, via the tail vein. The rats were decapitated at various times, the brains were removed and quickly dissected, and plasma metabolites were measured. Radioligand specificity, and P-glycoprotein involvement in brain uptake, was also assessed. 2-Cl-[(11)C]-(-)-NPA and [(11)C]-(-)-NPA were produced in high specific activity and purity. 2-Cl-[(11)C]-(-)-NPA accumulated slower in the striatum than [(11)C]-(-)-NPA, reaching maximum concentrations after 30 min. The maximal striatal uptake of 2-Cl-[(11)C]-(-)-NPA (standard uptake va...Continue Reading
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