A simple and efficient automated microvolume radiosynthesis of [18F]Florbetaben

BackgroundCurrent automated radiosynthesizers are generally optimized for producing large batches of PET tracers. Preclinical imaging studies, however, often require only a small portion of a regular batch, which cannot be economically produced on a conventional synthesizer. Alternative approaches are desired to produce small to moderate batches to reduce cost and the amount of reagents and radioisotope needed to produce PET tracers with high molar activity. In this work we describe the first reported microvolume method for production of [F-18]Florbetaben for use in imaging of Alzheimer's disease.ProceduresThe microscale synthesis of [F-18]Florbetaben was adapted from conventional-scale synthesis methods. Aqueous [F-18]fluoride was azeotropically dried with K2CO3/K-222 (275/383nmol) complex prior to radiofluorination of the Boc-protected precursor (80nmol) in 10 mu L DMSO at 130 degrees C for 5min. The resulting intermediate was deprotected with HCl at 90 degrees C for 3min and recovered from the chip in aqueous acetonitrile solution. The crude product was purified via analytical scale HPLC and the collected fraction reformulated via solid-phase extraction using a miniature C18 cartridge.ResultsStarting with 270100MBq (n =3) of [F-18]Fluoride, the method affords formulated product with 49 +/- 3% (decay-corrected) yield,>98% radiochemical purity and a molar activity of 338 +/- 55GBq/mu mol. The miniature C18 cartridge enables efficient elution with only 150 mu L of ethanol which is diluted to a final volume of 1.0mL, thus providing a sufficient concentration for in vivo imaging. The whole procedure can be completed in 55min.ConclusionsThis work describes an efficient and reliable procedure to produce [F-18]Florbetaben in quantities sufficient for large-scale preclinical applications. This method provides very high yields and molar activities compared to reported literature methods. This method can be applied to higher starting activities with special consideration given to automation and radiolysis prevention.