Microfluidics engineering for on-chip [18F]SiFA labeling of RGD peptides

Objectives In the past years the advantages of microfluidics for PET tracer syntheses have been demonstrated. However, to date chip-based microfluidics are not applicable for routine use due to high system complexity and cost. This study describes a PET chemistry platform with a view towards cost effective mass production. Its basic functionality is demonstrated by the first on-chip [18F]-labeling of a silicon fluoride acceptor (SiFA) derivatized αvβ3-integrin specific RGD peptide.

Methods The radiochemistry platform consists of a compact control device and a microfluidic chip. The system was engineered with a view towards high volume production techniques. Each chip contains reactors, valves as well as connectors and is chemically resistant to strong acids, bases, polar solvents and temperatures of up to 160°C. A QMA resin has been integrated into the system. Functionality of the device is demonstrated by the first fully automated on-chip [18F]-labeling of a silicon fluoride acceptor (SiFA) derivatized RGD peptide.

Results Aqueous 18-fluoride (600MBq, 500µl) and precursor (100µl) were loaded directly from low dead volume vials to the chip at >93% transfer efficiency for 18-fluoride with subsequent QMA trapping at >95% efficiency. Gas and acetonitrile drying was performed and the activity was eluted to an on-chip reaction chamber. There, SiFA labeling of the RGD peptide was completed after 15 minutes (RT) with >60% radiochemical yield. Overall process yield including all transfer and decay losses was >30%. The residual activity on-chip after product ejection was <5%.

Conclusions This study connects microfluidic chip materials, manufacturing techniques, chemical compatibility for radiochemistry and the implementation of functional elements such as valves into a complete design for cost effective mass manufacturing. The basic viability of this concept has been demonstrated by the first on-chip [18F]-labeling of a SiFA derivatized RGD peptide.

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