Fluorinated Coumarin Derivatives as Selective PET Tracer for MAO-B Imaging

Nan Wu; Xiaojun Zhang; Yuying Li; Jinming Zhang; Mengchao Cui

doi:10.1021/acs.jmedchem.4c01952

Fluorinated Coumarin Derivatives as Selective PET Tracer for MAO-B Imaging

J Med Chem. 2024 Dec 19. doi: 10.1021/acs.jmedchem.4c01952. Online ahead of print.

Authors

Nan Wu¹, Xiaojun Zhang², Yuying Li¹, Jinming Zhang², Mengchao Cui^{1

3}

Affiliations

¹ Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
² Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing 100853, China.
³ Center for Advanced Materials Research, Beijing Normal University, Zhuhai 519087, China.

PMID: 39699074
DOI: 10.1021/acs.jmedchem.4c01952

Abstract

Monoamine oxidase-B (MAO-B), predominantly exists on the outer mitochondrial membrane of astrocytes, serves as a crucial biomarker for reactive astrocytes during neuroinflammatory responses and various neurodegenerative diseases. In this study, we synthesized a series of fluorinated coumarin derivatives and evaluated their structure-activity relationship and subtype selectivity for MAO-B. Following this, the preclinical bioevaluation containing in vivo positron emission tomography (PET) imaging and ex vivo autoradiography studies led to the identification of the novel PET tracer, [¹⁸F]8, which demonstrated high affinity for MAO-B (IC₅₀ = 0.59 nM) and appreciable brain pharmacokinetics (SUV_max = 2.15 at 2 min, brain_2min/60min = 7.67) in rats. Furthermore, the radioactivates from [¹⁸F]8 in regions of MAO-B expression could be effectively inhibited by Selegiline. All these positive findings supported that [¹⁸F]8 is a promising candidate for MAO-B PET imaging, which merits further evaluation.