In vivo quantification of regional dopamine-D3 receptor binding potential of (+)-PHNO: Studies in non-human primates and transgenic mice

Eugenii A Rabiner, Mark Slifstein, Jose Nobrega, Christophe Plisson, Mickael Huiban, Roger Raymond, Mustansir Diwan, Alan A Wilson, Patrick McCormick, Gabriella Gentile, Roger N Gunn, Marc A Laruelle

Research output: Contribution to journalArticlepeer-review

124 Citations (Scopus)

Abstract

Examination of dopamine-D3 (D3) receptors with positron emission tomography (PET) have been hampered in the past by the lack of a PET ligand with sufficient selectivity for D3 over dopamine-D2 (D2) receptors. The two types co-localize in the brain, with D2 density significantly higher than D3, hence nonselective PET ligands inform on D2, rather than D3 status. [(11)C]-(+)-PHNO is a novel PET ligand with a preferential affinity for D3 over D2. We used the selective D3 antagonist, SB-277011 to dissect regional fractions of the [(11)C]-(+)-PHNO signal attributable to D3 and D2 in primate brain. The results were compared with quantitative autoradiography with (3)H-(+)-PHNO in wild-type, D2-knock-out, and D3-knock-out mice examined at baseline and following administration of SB-277011. Both sets of results converged to indicate a predominant D3-related component to (+)-PHNO binding in extra-striatal regions, with binding in the midbrain being entirely attributable to D3. The midbrain is thus an excellent target region to examine D3 receptor occupancy with [(11)C]-(+)-PHNO PET in vivo.
Original languageEnglish
Pages (from-to)782-793
Number of pages12
JournalSynapse
Volume63
Issue number9
Early online date1 Jun 2009
DOIs
Publication statusPublished - Sept 2009

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