title: Synthesis and initial PET imaging of new potential dopamine D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides.
abstract: D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D3 receptors. The new tracers 4,3,2-[11C]MMCs were prepared by O-[11C]methylation of corresponding precursors (E)-4,3,2-hydroxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-HMCs) using [11C]methyl triflate and isolated by the solid-phase extraction (SPE) purification procedure with 40-65% radiochemical yields, decay corrected to end of bombardment (EOB), and a synthesis time of 15-20 min. The PET dynamic studies of the tracers [11C]1a-c in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show that the brain uptake sequence was 4-[11C]MMC > 3-[11C]MMC > 2-[11C]MMC, which is consistent with their in vitro biological properties. The initial PET blocking studies of the tracers 4,3,2-[11C]MMCs with corresponding pretreatment drugs (E)-4,3,2-methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-MMCs, 1a-c) had no effect on 4,3,2-[11C]MMCs-PET rat brain imaging. These results suggest that the localization of 4,3,2-[11C]MMCs in rat brain is mediated by nonspecific processes, and the visualization of 4,3,2-[11C]MMCs-PET in rat brain is related to nonspecific binding.
authors.affiliation: Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202, USA.
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Gao
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Mock
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D008968:Molecular Conformation; D049268:Positron-Emission Tomography; D011869:Radioligand Assay / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000819:agonists*
chemical_list: D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D050637:Receptors, Dopamine D3