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

作者：Shoup Timothy M; Yokell Daniel L; Rice Peter A; Jackson Raul N; Livni Eli; Johnson Keith A; Brady Thomas J; Vasdev Neil^*

来源：Journal of Labelled Compounds and Radiopharmaceuticals, 2013, 56(14): 736-740.

DOI：10.1002/jlcr.3098

• T807
• tau
• PET
• fluorine-18

Fluorine-18 labeled 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([F-18]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 [F-18]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 [F-18]fluoride (K[F-18]/K-222) in DMSO at 130 degrees C over 10min the precursor is concurrently deprotected. Formulated [F-18]T807 was prepared in an uncorrected radiochemical yield of 14 +/- 3%, with a specific activity of 216 +/- 60GBq/mu mol (5837 +/- 1621mCi/mu mol) 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 [F-18]T807.

• 出版日期2013-12