An improved preparation of [¹⁸ F]AV-45 by simplified solid-phase extraction purification

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.