title: 11C-Fallypride: radiosynthesis and preliminary evaluation of a novel dopamine D2/D3 receptor PET radiotracer in non-human primate brain.
abstract: Fallypride [benzamide, 5-(3-fluoropropyl)-2,3-dimethoxy-N-[(2S)-1-(2-propenyl)-2-pyrrolidinyl]methyl]-, CAS RN 166173-78-0] is a selective dopamine D2/D3 receptor antagonist. Carbon-11 labeled fallypride may serve as a radiotracer for use in biomedical imaging technique positron emission tomography (PET). The precursor, 5-(3-fluoropropyl)-2-hydroxy-3-methoxy-N-[(2S)-1-(2-propenyl)-2-pyrrolidinyl]methyl]benzamide was synthesized from 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid, methyl ester in seven steps with approximately 10% overall chemical yield. Using this precursor (11)C-fallypride was produced by radiolabeling with (11)C-methyl iodide in 25-40% radiochemical yields with specific activities of 200-1000 Ci/mmol. PET imaging studies in nonhuman primates with (11)C-fallypride showed radiotracer localization in dopaminergic brain regions such as caudate, putamen, thalamus and cortex. This regional localization of (11)C-fallypride is similar to that observed previously for (18)F-fallypride. The results suggest (11)C-fallypride is a useful PET radiotracer for imaging dopamine D2/D3 receptors.
authors.affiliation: Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, CA 92697, USA. mukherjj@uci.edu
authors.forename: Jogeshwar
authors.initials: J
authors.lastname: Mukherjee
authors.forename: Bingzhi
authors.initials: B
authors.lastname: Shi
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
authors.forename: Sankha
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Tanjore K
authors.initials: TK
authors.lastname: Narayanan
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism; D018492:Dopamine Antagonists / Q000737:chemistry / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008253:Macaca mulatta; D011759:Pyrrolidines / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D001549:Benzamides; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3