Synthesis of [(18)F]FMISO in a flow-through microfluidic reactor: Development and clinical application.

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Chemical Engineering

Background:

• [(18)F]FMISO is a PET radiotracer used clinically for imaging tumor hypoxia.
• Optimizing radiochemical parameters is crucial for efficient [(18)F]FMISO preparation.
• Microfluidic reaction systems offer potential for improved synthesis control.

Purpose of the Study:

• To optimize radiochemical parameters for [(18)F]FMISO preparation using a microfluidic system.
• To evaluate precursor concentration, reaction temperature, and flow rate.
• To apply optimized conditions for large-scale batch production for clinical research.

Main Methods:

• A microfluidic reactor was used to test various reaction conditions (precursor concentration, temperature, flow rate).
• Radiochemical incorporation yields were determined using radio-TLC.
• Optimized conditions were applied to batch production, followed by standard hydrolysis.

Main Results:

• Optimal microfluidic parameters: 4 mg/mL precursor, 170 °C, 100 μL/min flow rate per reactant.
• Optimal hydrolysis: 2N HCl for 5 min at 100 °C.
• Large-scale production yielded [(18)F]FMISO with 28.4 ± 3.0% radiochemical yield, 119 ± 26 GBq/μmol specific activity, and >99% purity.

Conclusions:

• The NanoTek microfluidic system successfully prepared [(18)F]FMISO with high specific activity and purity.
• The flow chemistry approach enables efficient large-scale batch production for clinical research.
• The synthesized [(18)F]FMISO is suitable for human use and is currently employed in clinical studies.