RTI uses cookies to offer you the best experience online. By clicking “accept” on this website, you opt in and you agree to the use of cookies. If you would like to know more about how RTI uses cookies and how to manage them please view our Privacy Policy here. You can “opt out” or change your mind by visiting: http://optout.aboutads.info/. Click “accept” to agree.
Discovery of 6-(Fluoro-(18)F)-3-(1H-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)
Walji, A. M., Hostetler, E. D., Selnick, H., Zeng, Z., Miller, P., Bennacef, I., Salinas, C., Connolly, B., Gantert, L., Holahan, M., O'Malley, S., Purcell, M., Riffel, K., Li, J., Balsells, J., OBrien, J. A., Melquist, S., Soriano, A., Zhang, X., ... Coleman, P. J. (2016). Discovery of 6-(Fluoro-(18)F)-3-(1H-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). Journal of Medicinal Chemistry, 59(10), 4778-4789. https://doi.org/10.1021/acs.jmedchem.6b00166
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-F-18)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine, 6 ([F-18]-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.
