Synthesis of a PET tau tracer [(11)C]PBB3 for imaging of Alzheimer's disease.
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. [(11)C]PBB3 was prepared from either desmethyl-PBB3 or TBS-protected desmethyl-PBB3 with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with SPE in 20-25% and 15-20% radiochemical yield, respectively, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol with a total synthesis time of ~40-min from EOB.
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
Min
M
Wang
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
Mingzhang
M
Gao
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei 071002, China.
Zhidong
Z
Xu
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA. Electronic address: qzheng@iupui.edu.
Qi-Huang
QH
Zheng
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry*; D002250:Carbon Radioisotopes; D006801:Humans; D057054:Molecular Imaging; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000032:analysis*
C000592806:2-(4-(6-(methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo(d)thiazol-6-ol; D000631:Aminopyridines; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D016875:tau Proteins
Alzheimer’s disease (AD); Positron emission tomography (PET); Radiosynthesis; Tau tracer; [(11)C]PBB3