Radiosynthesis and quality control testing of the tau imaging positron emission tomography tracer [¹⁸F]PM‐PBB3 for clinical applications

Abstract

Recently, we produced ¹¹ C-labeled 2-((1E,3E)-4-(6-(methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ([¹¹ C]PBB3) as a clinically useful positron emission tomography (PET) tracer for in vivo imaging of tau pathologies in the human brain. To overcome the limitations (i.e., rapid in vivo metabolism and short half-life) of [¹¹ C]PBB3, we further synthesized ¹⁸ F-labeled 1-fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([¹⁸ F]PM-PBB3). [¹⁸ F]PM-PBB3 is also a useful tau PET tracer for imaging tau pathologies. In this study, we developed a routine radiosynthesis and quality control testing of [¹⁸ F]PM-PBB3 for clinical applications. [¹⁸ F]PM-PBB3 was synthesized by direct ¹⁸ F-fluorination of the tosylated derivative, followed by removal of the protecting group. [¹⁸ F]PM-PBB3 was obtained with sufficient radioactivity (25 ± 6.0% of the nondecay-corrected radiochemical yield at the end of synthesis, EOS), radiochemical purity (98 ± 0.6%), and molar activity (350 ± 94 GBq/μmol at EOS; n = 53). Moreover, [¹⁸ F]PM-PBB3 consistently retained >95% of radiochemical purity for 60 min without undergoing photoisomerization using a new UV-cutoff light (yellow light) fixed in the hot cell to monitor the synthesis. All the results of the quality control testing for the [¹⁸ F]PM-PBB3 injection complied with our in-house quality control and quality assurance specifications. We have accomplished >200 production runs of [¹⁸ F]PM-PBB3 in our facility for various research purposes.