11C-Fallypride: Radiosynthesis and preliminary evaluation of a novel dopamine D2/D3 receptor PET radiotracer in non-human primate brain

Article abstract of DOI:10.1016/j.bmc.2003.10.020

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 ¹¹C-fallypride was produced by radiolabeling with ¹¹C-methyl iodide in 25-40% radiochemical yields with specific activities of 200-1000 Ci/mmol. PET imaging studies in nonhuman primates with ¹¹C-fallypride showed radiotracer localization in dopaminergic brain regions such as caudate, putamen, thalamus and cortex. This regional localization of ¹¹C-fallypride is similar to that observed previously for ¹⁸F-fallypride. The results suggest ¹¹C-fallypride is a useful PET radiotracer for imaging dopamine D2/ D3 receptors.