A concise radiosynthesis of the tau radiopharmaceutical, [~18F]T807

摘要

Fluorine-18 labeled 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 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 FX_(FN) 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]/K_222) in DMSO at 130degC over 10min the precursor is concurrently deprotected. Formulated [~18F]T807 was prepared in an uncorrected radiochemical yield of 14 +-3%, with a specific activity of 216+-60GBq/mumol (5837 +-1621 mCi/fimol) at the end of synthesis (60min; n = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation that we anticipate will facilitate widespread clinical use of [~18F]T807.