In vivo DA D₁ receptor selectivity of NNC 112 and SCH 23390

Purpose: [¹¹C]NNC 112 and [¹¹C]SCH 23390 are selective positron emission tomography (PET) tracers for visualizing dopamine D₁ receptors. It is known that both have some affinity for serotonin 2A receptors, but previous studies have suggested this is negligible compared to D₁ affinity. We sought to verify this property in vivo. Procedures: Two baboons were scanned to measure the selectivity of both tracers with a displacement paradigm. Four baboons were scanned to directly assess [¹¹C] NNC 112 affinity for both receptors. Results: In vivo, D₁ to 5-HT_2A selectivity is six to fourteenfold, not 100-fold as previously reported by other investigators. Conclusion: We conclude that about 1/4 of the cortical signal of both [¹¹C]NNC 112 and [¹¹C]SCH 23390 is due to binding to 5-HT_2A receptors. If confirmed in humans, this suggests caution should be exercised when drawing conclusions from studies using either tracer. These results also indicate the need for more selective tracers for the D₁ receptor.