[11C]NNC 112 Selectivity for Dopamine D1 and Serotonin 5-HT2A Receptors: A PET Study in Healthy Human Subjects

Abstract

The dopamine D1 receptor antagonist radioligand [11C]NNC 112 has previously been reported to have 100-fold selectivity for the D1 receptor compared with the serotonin 5-HT2A receptor. In this study, we tested the selectivity by scanning seven healthy human research volunteers with [11C]NNC 112 before and after 2mg of the antipsychotic drug risperidone, a dose that putatively blocks all 5-HT2A receptors with negligible effect on D1 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 [11C]NNC 112 for D1 versus 5-HT2A as opposed to 100-fold selectivity. These results suggest caution in interpreting data from studies using this tracer to measure cortical D1 receptors as well as the need for more selective radioligands to assess cortical D1 receptors.