Synthesis and Autoradiography of Novel F‑18 Labeled Reversible Radioligands for Detection of Monoamine Oxidase B

• Published in: ACS chemical neuroscience Vol. 11; no. 24; pp. 4398 - 4404
• Main Authors: Nag, Sangram, Jia, Zhisheng, Svedberg, Marie, Jackson, Alex, Ahmad, Rabia, Luthra, Sajinder, Varnäs, Katarina, Farde, Lars, Halldin, Christer
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.12.2020
• Subjects: Medicin och hälsovetenskap; reversible radioligands; fluorine-18; MAO-B; autoradiography; PET
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.0c00631

Monoamine oxidase B (MAO-B) is an important enzyme regulating the levels of monoaminergic neurotransmitters. Selective MAO-B inhibitors have been labeled with carbon-11 or fluorine-18 to visualize the localization of MAO-B in vivo by positron emission tomography (PET) and thereby have been useful for studying neurodegenerative diseases. The aim of this study was to develop promising fluorine-18 labeled reversible MAO-B PET radioligands and their biological evaluation in vitro by autoradiography. Radiolabeling was achieved by classical one-step fluorine-18 nucleophilic substitution reaction. The stability and radiochemical yield was analyzed with HPLC. All five fluorine-18 labeled compounds were tested in human whole hemisphere autoradiography experiments. Five compounds (GEH200439, GEH200448, GEH200449, GEH200431A, and GEH200431B) were successfully radiolabeled with fluorine-18, and the incorporation yield of the fluorination reactions varied from 10 to 45% depending on the compound. The radiochemical purity was higher than 99% for all at the end of synthesis. Radioligands were found to be stable, with a radiochemical purity of >99% in a sterile phosphate buffered saline (pH = 7.4) over the duration of the study. The ARG binding density of only 18F-GEH200449 was consistent with known MAO-B expression in the human brain. Radiolabeling of five new fluorine-18 MAO-B reversible inhibitors was successfully accomplished. Compound 18F-GEH200449 binds specifically to MAO-B in vitro postmortem brain and could be a potential candidate for in vivo PET investigation.