Radiosynthesis of carbon-11 labeled PDE5 inhibitors as new potential PET radiotracers for imaging of Alzheimer's disease.

Abstract

To develop PET tracers for imaging of Alzheimer's disease, new carbon-11 labeled potent and selective PDE5 inhibitors have been synthesized. The reference standards (5) and (12), and their corresponding desmethylated precursors (6) and (13) were synthesized from methyl 2-amino-5-bromobenzoate and (4-methoxyphenyl)methanamine in multiple steps with 2%, 1%, 1% and 0.2% overall chemical yield, respectively. The radiotracers ([11C]5) and ([11C]12) were prepared from their corresponding precursors 6 and 13 with [11C]CH3OTf through O-11C-methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was in a range of 370-740 GBq/μmol.

• Authors: Fugui Dong, Jie Du, Caihong Miao, Limeng Jia, Wei Li, Min Wang, Qi-Huang Zheng, Zhidong Xu
• Journal: Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine (Appl Radiat Isot) Vol. 154 Pg. 108873 (Dec 2019) ISSN: 1872-9800 [Electronic] England
• PMID: 31470193 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Carbon Radioisotopes
• Carbon-11
• Phosphodiesterase 5 Inhibitors
• Radiopharmaceuticals
• Vardenafil Dihydrochloride

Topics

• Alzheimer Disease (diagnostic imaging, enzymology)
• Carbon Radioisotopes (chemistry)
• Chromatography, High Pressure Liquid
• Chromatography, Reverse-Phase
• Humans
• Phosphodiesterase 5 Inhibitors (chemical synthesis, chemistry)
• Positron-Emission Tomography (methods)
• Radioligand Assay
• Radiopharmaceuticals (chemical synthesis, chemistry)
• Vardenafil Dihydrochloride (analogs & derivatives, chemical synthesis, chemistry)