title: An improved synthesis of dopamine D2/D3 receptor radioligands [11C]fallypride and [18F]fallypride.
abstract: Improved syntheses of dopamine D(2)/D(3) receptor radioligands [(11)C]Fallypride and [(18)F]Fallypride are reported. The phenolic precursor (9) for C-11 labeling and the Fallypride (10) reference standard were synthesized from the starting material 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid methyl ester (1) in 7 and 8 steps with 16% and 5% overall chemical yields, respectively. The tosylated precursor (15) for F-18 labeling was synthesized from compound 1 in 5 steps with 32% overall chemical yield. An alternate synthetic approach for Fallypride has been developed using the same starting material 1 in 5 steps with 26% overall chemical yield. [(11)C]Fallypride ([(11)C]10) was prepared by O-[(11)C]methylation of the phenolic precursor with [(11)C]methyl triflate and purified with a semi-preparative HPLC method in 50-60% radiochemical yield, decay corrected to end of bombardment (EOB), based on [(11)C]CO(2), and 370+/-185 GBq/micromol specific radioactivity at EOB. [(18)F]Fallypride ([(18)F]10) was prepared by nucleophilic substitution of the tosylated precursor with K[(18)F]F/Kryptofix 2.2.2 and HPLC combined with solid-phase extraction (SPE) purification in variable (up to 50%) decay corrected radiochemical yield from K[(18)F]F and 111-222 GBq/micromol specific activity at EOB.
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: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Mock
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Glick-Wilson
authors.forename: Karmen K
authors.initials: KK
authors.lastname: Yoder
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis*; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D011759:Pyrrolidines / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism
chemical_list: D001549:Benzamides; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3