Automated Synthesis of [11C]PiB via [11CH3OTf]-as Methylating Agent for PET Imaging of β-Amyloid.

Aim: Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [¹¹C]PiB using commercially available dedicated [¹¹C]- Chemistry module from the synthesized precursor.

Background: [¹¹C]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 [¹¹C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [¹¹C]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 [¹¹C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [¹¹C]PiB with [¹¹C]CH₃OTf 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 [¹¹C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [¹¹C]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 [¹¹C]MeOTf as a methylating agent to synthesize [¹¹C]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.