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In vivo imaging of the D2 receptor with agonist radiotracers could provide important information on the high-affinity, functional state of the D2 receptor in schizophrenia and Parkinson's disease. Here the D2 agonist [11C]-(+)-PHNO was evaluated for use as an agonist PET radiotracer. In vitro, (+)-PHNO was shown, through competitive binding experiments and functional assays for D2 agonism, to be a potent full agonist at the D2 receptor. Ex vivo in rats, [11C]-(+)-PHNO readily crossed the blood-brain barrier and accumulated preferentially in the D2-rich striatum. [11C]-(+)-PHNO pharmacokinetics were rapid, with peak accumulation 5 min after tail-vein injection. The striatal binding of [11C]-(+)-PHNO was highly stereo selective, saturable, had pharmacology appropriate for D2 receptor binding and was sensitive to both increases and decreases in the concentration of endogenous dopamine. These characteristics make [11C]-(+)-PHNO a promising candidate for in vivo imaging of the high-affinity, functional state of the D2 receptor in humans using PET.
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Source: Masters Abstracts International, Volume: 44-06, page: 2775.
Thesis (M.Sc.)--University of Toronto, 2006.
Electronic version licensed for access by U. of T. users.
ROBARTS MICROTEXT copy on microfiche.
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