A Concise Radiosynthesis of the Tau Radiopharmaceutical 18FT807

摘要

Fluorine-18 labelled 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([¹⁸F]T807) is a potent and selective agent for imaging paired helical filaments of tau (PHF-tau) and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one-step method for the synthesis of [¹⁸F]T807 that is broadly applicable for routine clinical production using a GE Tracerlab^™ FXFN radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, tert-butyl 7-(6-nitropyridin-3-yl)-5H-pyrido[4,3-b]indole-5-carboxylate, as well as new HPLC separation conditions that enable a facile one-step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [¹⁸F]fluoride (K[¹⁸F]/K222) in DMSO at 130 °C over 10 min, the precursor is concurrently deprotected. Formulated [¹⁸F]T807 was prepared in an uncorrected radiochemical yield of 14 ± 3%, with a specific activity of 216 ± 60 GBq/μmol (5837 ± 1621 mCi/μmol) at the end of synthesis (60 min; n = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation which we anticipate will facilitate widespread clinical use of [¹⁸F]T807.