Positron emission tomography--examination of chemical transmission in the living human brain. Development of radioligands.

The imaging technique Positron Emission Tomography (PET) allows examination of chemical neurotransmission in brain. Of key importance for PET-research on neuroreceptors is the development of suitable radiolabelled tracers (ligands). This paper illustrates the multidisciplinary research activities necessary for ligand development. The selective D1- and D2-dopamine receptor antagonists SCH 23390 and raclopride (CAS 84225-95-6), respectively, were labelled with [3H] and characterized in biochemical studies in vitro on human brain homogenates and in autoradiographic studies on cryosections from human hemispheres. The experimental information was used to interpret and support the PET-findings with [11C]-labelled SCH 23390 and raclopride in vivo in humans. In conclusion, these ligands can be used to quantitatively examine dopamine receptors in the human basal ganglia in vivo. An applied study for PET-determination of D1- and D2-dopamine receptor occupancy during antipsychotic drug treatment indicates that the D2-dopamine receptor and possibly also the D1-dopamine receptor are targets for neuroleptic drug action.