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‐((1 E ,3 E )‐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‐((1 E ,3 E )‐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.