High-efficiency [18F]fluoride pre-concentration using a laser-micromachined anion-exchange micro-cartridge

Abstract

Background: The use of radiopharmaceuticals labelled with fluorine-18 in non-invasive imaging, particularly in Positron Emission Tomography (PET), increased significantly during the last decade. However, traditional nucleophilic fluorination synthesis methods in most cases require azeotropic drying steps, leading to loss of activity and increased synthesis time. Microfluidic devices offer improvements with shorter reaction times, higher elution efficiency, and reduced reagent quantities. Results: We developed a novel micro-cartridge for [18F]fluoride trapping and elution, etched in borosilicate optical glass (BK7) using ultrashort laser pulse machining. The micro-cartridge has a bead volume of 17 µL and a maximum capacity of 8.5 mg for anion exchange resin. The micro-cartridge, without the need for QMA preconditioning, exhibited an overall trapping efficiency and recovery efficiency (RE) of (94.09 ± 0.12)% using an activity exceeding 123 GBq of [18F]fluoride. This RE was obtained using 100 µL of a standard solution of anhydrous acetonitrile with Kryptofix 2.2.2, containing only 5 µL of water and 5.4 µmol of K2CO3 for [18F]fluoride elution. This solution was employed directly in the radiosynthesis of [18F]fluoromisonidazole ([18F]FMISO), resulting in a 100% radiochemical conversion (RCC) to THP-protected [18F]FMISO within 10 min at 110 °C. Conclusions: The developed micro-cartridge provides a novel tool for integrating microfluidic chips into conventional cassettes, facilitating more efficient radiopharmaceutical preparation.