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

• Published in: Bioorganic & medicinal chemistry letters Vol. 25; no. 15; pp. 2953 - 2957
• Main Authors: Gao, Mingzhang, Wang, Min, Zheng, Qi-Huang
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.08.2015; Elsevier
• Subjects: [18F]T807; Alzheimer Disease - diagnostic imaging; Alzheimer’s disease (AD); Automation; Carbolines - chemical synthesis; Carbolines - chemistry; Chemistry; Chemistry Techniques, Synthetic - methods; Chemistry, Medicinal; Chemistry, Organic; Fluorine Radioisotopes - chemistry; Halogenation; Humans; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Positron emission tomography (PET); Positron-Emission Tomography; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Science & Technology; tau Proteins - analysis; Tau tracer; Automation; Positron emission tomography (PET); Alzheimer’s disease (AD); Tau tracer; [18F]T807; CONCISE; [F-18]T807; RADIOPHARMACEUTICALS; RADIOSYNTHESIS; Alzheimer's disease (AD); AGENTS; PATHOLOGY; [F]T807
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.05.035

[Display omitted] 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 37–370GBq/μmol.