Highly efficient solid phase supported radiosynthesis of [¹¹ C]PiB using tC18 cartridge as a "3-in-1" production...

Pittsburgh compound B ([¹¹ C]PiB) is the gold standard positron emission tomography (PET) tracer for the in vivo imaging of amyloid plaques. Currently, it is synthesized by either solution chemistry or using a "dry loop" approach followed by HPLC purification within 30 minutes starting from [¹¹ C]CO₂ . Here, we report a novel, highly efficient solid phase supported carbon-11 radiolabeling procedure using commercially available disposable tC18 cartridge as a "3-in-1" entity: reactor, purifier, and solvent replacement system. [¹¹ C]PiB is synthesized by passing gaseous [¹¹ C]CH₃ OTf through a tC18 cartridge preloaded with a solution of precursor. Successive elution with aqueous ethanol solutions allows for nearly quantitative separation of the reaction mixture to provide chemically and radiochemically pure PET tracer. [¹¹ C]PiB suitable for human injection is produced within 10 minutes starting from [¹¹ C]CH₃ OTf (20 min from [¹¹ C]CO₂ ) in 22% isolated yield not corrected for decay and molar activity of 190 GBq/μmol using 0.2 mg of precursor. This technique reduces the amount of precursor and other supplies, avoids use of preparative HPLC and toxic solvents, and decreases the time between consecutive production batches. Solid phase supported technique can facilitate [¹¹ C]PiB production compliant with Good Manufacturing Practice (GMP) and improve synthesis reliability.