Regional distribution of high and low affinity states of dopamine D2/3 receptor binding in humans: A PET study using [11C]MNPA and [11C]raclopride

Purpose: Dopaminergic neurotransmission is of major interest in the pathophysiology of schizophrenia, and the effects of antipsychotic drugs have generally been considered to be mediated by dopamine D2 receptor blockade. Early in vitro studies indicated that dopamine D2/3 receptor has two interconvertible states, that is, high-affinity state (D2/3) and low-affinity state (D2/3). D2/3 is thought to reflect a functional state of endogenous dopamine. Themixed bindings of both D2/3 and D2/3 in these regions have beenmeasured by the use of dopamine D2/3 antagonist radioligands such as [C]raclopride. D2/3 binding can be measured with dopamine D2/3 agonist radioligands such as [C]MNPA. However, little is known about the regional differences in distribution between D2/3and D2/3 bindings. In the present study, we measured D2/3 binding and the mixed bindings of D2/3 and D2/3 using [C]MNPA and [C]raclopride in same human subjects. The respective regional bindings of [C]MNPA and [C]raclopride were compared.