An improved synthesis of dopamine D2/D3 receptor radioligands [11C]fallypride and [18F]fallypride.
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.
Gao
Mingzhang
M
Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202, USA.
Wang
Min
M
Mock
Bruce H
BH
Glick-Wilson
Barbara E
BE
Yoder
Karmen K
KK
Hutchins
Gary D
GD
Zheng
Qi-Huang
QH
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
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