Radiosynthesis of [¹¹C]PiB for the loop labeling method using a cassette-type multipurpose automatic synthesizer module

Objectives: Recently, we developed a benzofuran derivative for the imaging of β-amyloid (Aβ) plaques, 5-(5-(2-(2-(2-[¹⁸F]fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine ([¹⁸F]FPYBF-2) (Ono et al., J Med Chem, 54, 2971-9 2011). To compare with [¹⁸F]FPYBF-2 study in clinical practice, the aim of this study was to assess the radiosynthesis, quality control and safety assessment of the loop labeling method using a cassette-type multipurpose automatic synthesizer module for radiosynthesis of [¹¹C]Pittsburg compound B ([¹¹C]PiB).

Methods: The radiosynthesis of [¹¹C]PiB was performed on a hybrid synthesizer, cassette-type multipurpose automatic synthesizer module (JFE Engineering Corporation). [¹¹C]Methyl triflate was trapped in a loop of sterilized spiral type (Lectro-Cath, Vigon) precharged with 1 mg of precursor, 2-(4’-aminophenyl)-6-hydroxybenzothiazole in 60 µL of Cyclohexanone and reacted for 1 min at room temperature after radioactivity peaks in the loop. After purification of the crude product by HPLC, [¹¹C]PiB was eluted with 2.5% ethanol in saline. The quality control tests of final products and safety assessment were performed.

Results: [¹¹C]PiB for the loop labeling method was produced with radioactivity of 12.2 ± 0.9 GBq, total synthesis time of 26.6 ± 0.2 min, radiochemical yield (decay uncorrected) of 38.7 ± 1.5 %, radiochemical purity of > 99.9 % and specific activity of 95.5 ± 10.1 GBq/µmol. The products satisfied the relevant quality standard such as the Quality Control of [¹⁸F]FDG. There was no harmful finding at a single dose toxicity test (radiolabeled final products).

Conclusion: By the loop labeling method using a cassette-type multipurpose automatic synthesizer module, the synthesis of [¹¹C]PiB for clinical grade was successfully implemented in our study with healthy volunteers and patients with dementia.