title: [11C]NNC 112 selectivity for dopamine D1 and serotonin 5-HT(2A) receptors: a PET study in healthy human subjects.
abstract: The dopamine D(1) receptor antagonist radioligand [(11)C]NNC 112 has previously been reported to have 100-fold selectivity for the D(1) receptor compared with the serotonin 5-HT(2A) receptor. In this study, we tested the selectivity by scanning seven healthy human research volunteers with [(11)C]NNC 112 before and after 2 mg of the antipsychotic drug risperidone, a dose that putatively blocks all 5-HT(2A) receptors with negligible effect on D(1) receptors. We found that specific binding in cortical regions was reduced by 20% to 30%, whereas the striatum showed no change. Based on the known relative densities of these receptors in humans, our results suggest 5- to 10-fold selectivity of [(11)C]NNC 112 for D(1) versus 5-HT(2A) as opposed to 100-fold selectivity. These results suggest caution in interpreting data from studies using this tracer to measure cortical D(1) receptors as well as the need for more selective radioligands to assess cortical D(1) receptors.
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York, USA. mms218@columbia.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.forename: Robyn
authors.initials: R
authors.lastname: Gonzales
authors.forename: William G
authors.initials: WG
authors.lastname: Frankle
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D018967:Risperidone / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D001572:Benzofurans; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; C077123:NNC 112; D018967:Risperidone