An improved synthesis of dopamine D₂/D₃ receptor radioligands [¹¹C]fallypride and [¹⁸F]fallypride

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• 作者：Mingzhang Gao ; Min Wang ; Bruce H. Mock ; Barbara E. Glick-Wilson ; Karmen K. Yoder ; Gary D. Hutchins ; Qi-Huang Zheng
• 关键词：[¹¹C]Fallypride ; [¹⁸F]Fallypride ; Positron emission tomography (PET) ; Imaging ; Dopamine D₂/D₃ receptor
• 刊名：Applied Radiation and Isotopes
• 出版年：2010
• 出版时间：June 2010
• 年：2010
• 卷：68
• 期：6
• 页码：1079-1086
• 全文大小：252 K

文摘

Improved syntheses of dopamine D₂/D₃ receptor radioligands [¹¹C]Fallypride and [¹⁸F]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. [¹¹C]Fallypride ([¹¹C]10) was prepared by O-[¹¹C]methylation of the phenolic precursor with [¹¹C]methyl triflate and purified with a semi-preparative HPLC method in 50–60 % radiochemical yield, decay corrected to end of bombardment (EOB), based on [¹¹C]CO₂, and 370±185 GBq/μmol specific radioactivity at EOB. [¹⁸F]Fallypride ([¹⁸F]10) was prepared by nucleophilic substitution of the tosylated precursor with K[¹⁸F]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[¹⁸F]F and 111–222 GBq/μmol specific activity at EOB.