Fully automated synthesis of [18F]T807, a PET tau tracer for Alzheimer’s disease

Abstract

The authentic standard T807 and its nitro-precursor T807P as well as t-Boc-protected T807P precursor for radiolabeling were synthesized from (4-bromophenyl)boronic acid, 3-bromo-4-nitropyridine and 3-bromo-6-nitropyridine with overall chemical yield 27% in three steps, 4–7% in three to five steps, and 3–8% in four to five steps, respectively. [18F]T807 was synthesized from T807P by the nucleophilic [18F]fluorination with K[18F]F/Kryptofix 2.2.2 in DMSO at 140 °C followed by reduction with Fe powder/HCOOH through manual synthesis with 5–10% decay corrected radiochemical yield in two steps. [18F]T807 was also synthesized from t-Boc-protected T807P by a concurrent [18F]fluorination and deprotection with K[18F]F/Kryptofix 2.2.2 in DMSO at 140 °C and purified by HPLC-SPE method in a home-built automated [18F]radiosynthesis module with 20–30% decay corrected radiochemical yield in one step. The specific activity of [18F]T807 at end of bombardment (EOB) was 37–370 GBq/μmol.