Solvent resistant microfluidic platform for complete SiFA-based PET tracer synthesis

Objectives To date, chip-based microfluidic systems expose a high system complexity to the operator. This study describes an easy to use PET chemistry platform that integrates 18-fluoride phase transfer, radiolabeling and purification while maintaining a view towards cost effective mass production of microfluidic chips. Proof-of-concept is demonstrated by the full synthesis of a Gastrin-releasing peptide receptor binding PEGylated Bombesin BN(7-14)-derivative ([18F]PESIN) PET tracer.

Methods The platform consists of a compact control device and a microfluidic chip. The chip contains reactors, valves, resins, a connector interface and is chemically resistant to strong acids, bases, polar solvents and temperatures of up to 150°C. Custom chips are prototyped and employed on the platform for the complete synthesis of [18F]PESIN.

Results All required reagents including 18-fluoride are gas pressure loaded from vials to the chip. Phase transfer, radiolabeling, purification and product output are performed on the platform. The full synthesis resulted in 33% (±3%) (n=4) of the initial fluoride-18 activity transferred into the [18F]PESIN product (not time corrected) at >99% radiochemical purity (RCP) and 34 min. total process time (cartridges external to chip). A first non-optimized run with on-chip cartridges resulted in 12% activity transfer to purified [18F]PESIN product (not time corrected) at >99% RCP.

Conclusions This study connects microfluidic chip materials, manufacturing techniques, chemical compatibility for radiochemistry and the implementation of all functional elements required for a SiFA-based radiosynthesis into a compact platform. The platform is easy to use and ready for implementation of existing and future PET tracer synthesis routines.

Research Support The authors gratefully acknowledge the financial support from the Leading-Edge Cluster m4 and the German Federal Ministry of Education and Research.