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

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• 作者：Abbas M. Walji ; Eric D. Hostetler ; Harold Selnick ; Zhizhen Zeng ; Patricia Miller ; Idriss Bennacef ; Cristian Salinas ; Brett Connolly ; Liza Gantert ; Marie Holahan ; Stacey O’Malley ; Mona Purcell ; Kerry Riffel ; Jing Li ; Jaume Balsells ; Julie A. OBrien ; Stacey Melquist ; Aileen Soriano ; Xiaoping Zhang ; Aimie Ogawa ; Serena Xu ; Elizabeth Joshi ; Joseph Della Rocca ; Fred J. Hess ; Joel Schachter ; David Hesk ; David Schenk ; Arie Struyk ; Kerim Babaoglu ; Talakad G. Lohith ; Yaode Wang ; Kun Yang ; Jianmin Fu ; Jeffrey L. Evelhoch ; Paul J. Coleman
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：May 26, 2016
• 年：2016
• 卷：59
• 期：10
• 页码：4778-4789
• 全文大小：659K
• 年卷期：0
• ISSN：1520-4804

文摘

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-¹⁸F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine, 6 ([¹⁸F]-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.