Positron Emission Tomography (PET) Study: The Effects of 6R-L-Erythro-5,6,7,8-Tetrahydrobiopterin (R-THBP, SUN 0588) on the Central Dopamine D1, D2 and D3 Receptors in Rhesus Monkey

Among the brain imaging techniques, X-ray computed tomography (CT) and magnetic resonance imaging (MRI) give morphological images, but positron emission tomography (PET), which gives functional images, allows monitoring non-invasively of energy metabolism, local blood flow, some enzyme reactions and several types of receptor bindings1. The developments of PET technique and the selective radioligands has potentiated to improve our knowledge of the physiology of neurotransmitter systems and to monitor drug action by directly measuring changes in energy metabolism and receptor occupancy as results of altered storage pool of neurotransmitter, neurotransmitter release, re-uptake, etc. in human and non human primates2. Especially, the dopaminergic system has been well studied by PET, since the dopaminergic terminals are highly concentrated in the striatum and the size of the striatum is suitable for spatial resolution of PET. Within the components of dopaminergic system, measurable postsynaptic components by PET are D1 and D2 receptors,3 and measurable presynaptic components are turnover of dopamine4 and dopamine re-uptake site.5 Furthermore, in this paper, we attempt to analyse the dopamine D3 receptor by PET using the selective ligand (+)[11C]UH232 (cis-(+)-5-methoxy-l-methyl-2-(di-n-propylamino)tetralin), which was characterized as an acting dopamine autoreceptor antagonist with the biochemical and behavioral profile.6 The aim of the present study is to clarify the effects of peripherally administered R-THBP (SUN 0588, the chemically synthesized dihydrochlorides salt of R-THBP, Suntory Limited) on the dopamine D1, D2 and D3 receptor systems in the living rhesus monkey brain using PET technique.