Automated Synthesis of [C]PiB [CHOTf]-as Methylating Agent for PET Imaging of β-Amyloid.

AIM

Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [C]PiB using commercially available dedicated [C]- Chemistry module from the synthesized precursor.

BACKGROUND

[C]PiB is a promising radiotracer for PET imaging of β-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use.

METHODS

The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods were characterized all synthesized compounds. The fully automated [C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [C]PiB with [C]CHOTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life.

RESULTS

The precursor for radiosynthesis of [C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/μmol range.

CONCLUSION

A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [C]MeOTf as a methylating agent to synthesize [C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.