Discovery of 6-(Fluoro- 18 F )-3-(1 H -pyrrolo[2,3- c ]pyridin-1-yl)isoquinolin-5-amine ([ 18 F]-MK-6240): A Positron Emission Tomography (PET) Imaging Agent for Quantification of Neurofibrillary Tangles (NFTs)

作者：Abbas M. Walji, Eric D. Hostetler, Harold G. Selnick, Zhizhen Zeng, Patricia Miller, Idriss Bennacef, Cristian A Salinas, Brett Connolly, Liza T. Gantert, Marie A. Holahan, Stacey S O'Malley, Mona L. Purcell, Kerry A. Riffel, Jing Li, Jaume Balsells, Julie A. O’Brien, Stacey Melquist, Aileen Soriano, Xiaoping Zhang, Aimie M. Ogawa, Serena Xu, Elizabeth Joshi, Joseph Della Rocca, Fred J. Hess, Joel B. Schachter, David Hesk, David Schenk, Arie F. Struyk, Kerim Babaoglu, Talakad Goolaiah Lohith, Yaode Wang, Kun Yang, Jianmin Fu, Jeffrey L. Evelhoch, Paul J. Coleman · 发表于：Journal of Medicinal Chemistry · 年份：2016 · DOI：10.1021/acs.jmedchem.6b00166 · 被引用次数：185 · 研究领域：Cancer Treatment and Pharmacology、Advanced Neuroimaging Techniques and Applications、Medical Imaging Techniques and Applications

Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery of new disease modifying therapeutics targeting tau pathology. Herein, we present the discovery of 6-(fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine, 6 ([(18)F]-MK-6240), as a novel PET tracer for detecting NFTs. 6 exhibits high specificity and selectivity for binding to NFTs, with suitable physicochemical properties and in vivo pharmacokinetics.