PHENYX – A flexible pipetting-based platform for automated microvolume radiochemistry

Abstract

Recent droplet-based radiochemistry platforms have enabled reactions in < 10 µL volumes, providing many advantages including minimal reagent consumption, fast synthesis times, high yields, high molar activity, and scalable production amount. However, in the open droplet format there can be at times unwanted evaporation, or loss of activity as volatile species. To address this limitation, we developed a pipette-based radiosynthesizer platform, in which microvolume reactions are performed in a small well that can be sealed using a removable heated lid. The overall system comprises a pipettor mounted on a XYZ motion gantry to access a pipette tip rack, specialized pipette attachments, and a disposable cassette. All synthesis operations are performed by the pipette, including trap and release of [18F]fluoride from the QMA cartridge, liquid transfers among reservoirs and the reactor, and installation or removal of the heated lid, enabling a wide range of radiosynthesis protocols to be implemented. As a proof-of-concept demonstration, [18F]Fallypide was synthesized on the platform. Up to 2 mL of aqueous [18F]fluoride (2 – 540 MBq) was concentrated to ∼ 34 μL by trapping on a preconditioned micro-QMA cartridge (3 mg resin) and eluting with TBAHCO3 (0.35 μmol). The concentrated radioisotope was evaporated in the Reactor, and then 8 μL of precursor solution (0.62 μmol in MeCN/thexyl alcohol) was added and heated at 110 °C for 7 min. After collection and analytical-scale HPLC purification, the radiochemical yield was 71 ± 6% (n = 3), and the product exhibited high radiochemical purity (>99%) and molar activity of 290–670 GBq/μmol.