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Rabiner, E.A. et al.

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,

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

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.[1]

References

In vivo quantification of regional dopamine-D3 receptor binding potential of (+)-PHNO: Studies in non-human primates and transgenic mice. Rabiner, E.A., Slifstein, M., Nobrega, J., Plisson, C., Huiban, M., Raymond, R., Diwan, M., Wilson, A.A., McCormick, P., Gentile, G., Gunn, R.N., Laruelle, M.A. Synapse (2009) [Pubmed]

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