[¹¹C]NNC 112 selectivity for dopamine D₁ and serotonin 5-HT_2A receptors: A PET study in healthy human subjects

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-HT_2A receptor. In this study, we tested the selectivity by scanning seven healthy human research volunteers with [¹¹C]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 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-HT_2A 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.