Positron emission tomography imaging of dopamine D2 receptors using a highly selective radiolabeled D2 receptor partial agonist

A series of microPET imaging studies were conducted in anesthetized rhesus monkeys using the dopamine D2-selective partial agonist, [11C]SV-III-130. There was a high uptake in regions of brain known to express a high density of D2 receptors under baseline conditions. Rapid displacement in the caudate and putamen, but not in the cerebellum, was observed after injection of the dopamine D2/3 receptor nonselective ligand S(−)-eticlopride at a low dosage (0.025mg/kg/i.v.); no obvious displacement in the caudate, putamen and cerebellum was observed after the treatment with a dopamine D3 receptor selective ligand WC-34 (0.1mg/kg/i.v.). Pretreatment with lorazepam (1mg/kg, i.v. 30min) to reduce endogenous dopamine prior to tracer injection resulted in unchanged binding potential (BP) values, a measure of D2 receptor binding in vivo, in the caudate and putamen. d-Amphetamine challenge studies indicate that there is a significant displacement of [11C]SV-III-130 by d-Amphetamine-induced increases in synaptic dopamine levels. ► We synthesized a novel dopamine D2 receptor radiotracer, [11C]SV-III-130. ► We conducted microPET imaging of dopamine D2 receptors using [11C]SV-III-130. ► [11C]SV-III-130 binding can be displaced by D2/3 ligand S(−)-eticlopride. ► Dopamine depletion via lorazepam treatment didn't change the binding potential. ► d-Amphetamine induced dopamine increase displaced [11C]SV-III-130 binding.