Fully automated radiosynthesis of [18F]mG4P027 for mGluR4 imaging

Background

Fluorine-18 labeled N-(4-chloro-3-(((fluoro-¹⁸F)methyl-d₂)thio)phenyl)picolinamide, [¹⁸F]mG4P027, is a potent positron emission tomography (PET) radiotracer for mGluR4. Our previous in vitro and in vivo evaluations have demonstrated that this tracer is promising for further translational studies. However, automated radiosynthesis process poses significant challenges that need to be addressed.

Methods

The automated radiosynthesis was performed using the TRACERlab FX2N module, which comprises two distinct reactors capable of accommodating the two-step reactions. Several problem-solving strategies were employed to overcome challenges during the automation process. This included modifications to the reaction solvents, reaction conditions, use of a scavenger, drying methods, and the handling of the precursor.

Results

The use of n-Bu₄NN₃ for scavenging excess compound 1 along with an efficient drying procedure played a key role in the success of the radiosynthesis. The water was successfully removed by using a different duct to overcome the water sensitivity for the second reaction.

Conclusions

Significant modifications were made to the manual process by carefully examining this process and addressing the root causes of the challenges associated with its automation. We successfully implemented automated radiosynthesis using the TRACERlab FX2N module and consequently, obtained a high-purity radiolabeled [¹⁸F]mG4P027 in high yield, meeting the requirements for future human studies.