Radiosynthesis of GlyT1 PET tracer [¹⁸F]CFPyPB using NanoTek Microfluidic Synthesizer and an external computer-controlled vial heater

Objectives [¹⁸F]CFPyPB is a potent and selective PET tracer for GlyT1 which is an attractive target for schizophrenic drug development. We tested the labeling with our fully automated microfluidic system aiming to make it available for drug evaluation in our imaging facility.

Methods Our NanoTek microfluidic system was recently self-upgraded to include a second concentrator, an HPLC system, and a formulation system for full automated operation. The labeling was first tested at different temperature / flow rate with the microfluidic reactor. Later a computer-controlled vial heater was self-made. The heater was coupled with the NanoTek system for high temperature reactions. After drying of F-18 through concentrator 1, activity was re-taken into DMSO and dispensed to a V-vial with the precursor in the vial heater through Pump 3. On the computer screen heating can be started and stopped for cooling. The reaction was diluted with HPLC solvent and loaded into HPLC through concentrator 2. A click on the screen sent a signal to start HPLC. There are real-time UV and radiation chromatograms on the screen. The [¹⁸F]CFPyPB peak was collected into a flask with a V-bottom containing sterile water. The diluted HPLC cut was pushed through a C18 SPE cartridge. The retained tracer was rinsed with sterile water and then eluted into a final product vial with 1 mL ethanol followed by 10 mL saline.

Results Discovery runs with the microfluidic reactor gave no product at 150 - 180⁰C with a normal flow rate. A radiochemical yield of 7 - 17% was obtained at 190 - 200⁰C with a very slow flow rate. Using the self-made vial heater, the yield varied from 21 to 40% at 165 - 180⁰C. Under above conditions, the final formulated product was obtained at an uncorrected yield of 4 - 6%.

Conclusions Extremely slow flow rate of microfluidic reactions is not acceptable for a full synthesis. For high temperature reactions, such as synthesis of [¹⁸F]CFPyPB, an external computer-controlled vial heater provides the best option to achieve the synthesis conveniently.

Research Support All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.