Synthesis of a PET tau tracer [11C]PBB3 for imaging of Alzheimer’s disease

• Published in: Bioorganic & medicinal chemistry letters Vol. 25; no. 20; pp. 4587 - 4592
• Main Authors: Wang, Min, Gao, Mingzhang, Xu, Zhidong, Zheng, Qi-Huang
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.10.2015; Elsevier
• Subjects: [11C]PBB3; Alzheimer Disease - diagnosis; Alzheimer Disease - metabolism; Alzheimer’s disease (AD); Aminopyridines - chemical synthesis; Aminopyridines - chemistry; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Carbon Radioisotopes; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Humans; Life Sciences & Biomedicine; Molecular Imaging; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Positron emission tomography (PET); Positron-Emission Tomography; Radiosynthesis; Science & Technology; tau Proteins - analysis; Tau tracer; Positron emission tomography (PET); Alzheimer’s disease (AD); Tau tracer; [11C]PBB3; Radiosynthesis; ROUTE; RADIOLIGAND; FULLY AUTOMATED SYNTHESIS; ACROLEIN-DIETHYL-ACETAL; NEUROFIBRILLARY PATHOLOGY; Alzheimer's disease (AD); RADIOTRACERS; PROBES; [C-11]PBB3; 1ST RADIOSYNTHESIS; AGENTS; CINNAMALDEHYDES; [C]PBB3
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.08.053

[Display omitted] The authentic standard PBB3 and its precursor N-desmethyl-PBB3 as well as TBS-protected N-desmethyl-PBB3 precursor for radiolabeling were synthesized from 5-bromo-2-nitropyridine, acrolein diethyl acetal, 6-methoxy-2-methylbenzothiazole, and diethylchlorophosphate with overall chemical yield 1% in six steps, 2% in five steps, and 1% in six steps, respectively. [11C]PBB3 was prepared from either desmethyl-PBB3 or TBS-protected desmethyl-PBB3 with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 20–25% and 15–20% radiochemical yield, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370–1110GBq/μmol with a total synthesis time of ∼40-min from EOB.