Dose-on-demand production of diverse 18F-radiotracers for preclinical applications using a continuous flow microfluidic system

Abstract

IntroductionThe production of 18F-radiotracers using continuous flow microfluidics is under-utilized due to perceived equipment limitations. We describe the dose-on-demand principle, whereby the back-to-back production of multiple, diverse 18F-radiotracers can be prepared on the same day, on the same microfluidic system using the same batch of [18F]fluoride, the same microreactor, the same HPLC column and SPE cartridge to obtain a useful production yield. Methods[18F]MEL050, [18F]Fallypride and [18F]PBR111 were radiolabeled with [18F]fluoride using the Advion NanoTek Microfluidic Synthesis System. The outlet of the microreactor was connected to an automated HPLC injector and following the collection of the product, SPE reformulation produced the 18F-radiotracer in <10% ethanolic saline. A thorough automated cleaning procedure was implemented to ensure no cross-contamination between radiotracer synthesis. ResultsThe complete productions for [18F]MEL050 and [18F]Fallypride were performed at total flow rates of 20μL/min, resulting in 40±13% and 25±13% RCY respectively. [18F]PBR111 was performed at 200μL/min to obtain 27±8% RCY. Molar activities for each 18F-radiotracer were >100GBq/μmol and radiochemical purities were >97%, implying that the cleaning procedure was effective. ConclusionsUsing the same initial solution of [18F]fluoride, microreactor, HPLC column and SPE cartridge, three diverse 18F-radiotracers could be produced in yields sufficient for preclinical studies in a back-to-back fashion using a microfluidic system with no detectable cross-contamination.