An improved preparation of [18F]AV‐45 by simplified solid‐phase extraction purification. (30th January 2020)

• Record Type: Journal Article
• Authors: Zhang, Lifang; Zhang, Aili; Yao, Xinyue; Zhang, Yan; Liu, Futao; Hong, Haiyan; Zha, Zhihao; Liu, Yajing; Wu, Zehui; Qiao, Jinping; Zhu, Lin; Kung, Hank F.
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 63:Number 3(2020)
• Page Start: 108
• Page End: 118
• Publication Date: 2020-01-30
• Subjects: automated radiosynthesis -- florbetapir f18 -- fluorine‐18 -- solid‐phase extraction purification; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3813
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract: Amyvid (florbetapir f18, [ 18 F]AV‐45, [ 18 F]5 ) was the first FDA‐approved positron emission tomography imaging agent targeting β‐amyloid (Aβ) plaques for assisting the diagnosis of Alzheimer disease. This work aimed to improve the [ 18 F]AV‐45 ([ 18 F]5 ) preparation by using solid‐phase extraction (SPE) purification. [ 18 F]AV‐45 ([ 18 F]5 ) was synthesized by direct nucleophilic radiofluorination of O ‐tosylated precursor (1 mg) at 120°C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N ‐Boc protecting group. Purification was accomplished by loading the crude reaction mixture to a cartridge (Oasis HLB 3 cc) and eluting with different combinations of solvents. This method removed the chemical impurity while leaving [ 18 F]AV‐45 ([ 18 F]5 ) on the cartridge. The final dose was eluted by ethanol. [ 18 F]AV‐45 ([ 18 F]5 ) was produced within 51 minutes (radiochemical yield 42.7 ± 5.9%, decay corrected, n = 3), and the radiochemical purity was greater than 95%. Total chemical impurity per batch (24.1 ± 2.7 μg per batch) was below the limit described in the package insert of Amyvid, florbetapir f18 (chemical mass: less than 50 μg/dose). In summary, [ 18 F]AV‐45 ([ 18 F]5 ) was produced efficiently and reproducibly using a cartridge‐based SPE purification. This method brings the process closer for routine preparation, similar to the commercially used [ 18 F]FDG. Abstract : [ 18 F]AV‐45 was prepared with a high radiochemical yield (43 ± 6%, decay corrected) and high radiochemical purity (greater than 95%) in 51 minutes. Total chemical impurity per batch (24.1 μg/batch) was below the limit described in the package insert of Amyvid, florbetapir f18, (chemical mass: less than 50 μg/dose). This cartridge‐based solid‐phase purification process might be suitable for routine preparation in clinical application.