Myelin is the protective sheath that surrounds nerves in vertebrates to protect axons, which thereby facilitates impulse conduction. Damage to myelin is associated with many neurodegenerative diseases such as multiple sclerosis and also includes spinal cord injury (SCI). The small size of the spinal cord poses formidable challenges to in vivo monitoring of myelination, which we investigated via conducting a structure-activity relationship study to determine the optimum positron-emitting agent to use for imaging myelin using positron emission tomography (PET). From these studies, [F]PENDAS was identified as the lead agent to use in conjunction with PET imaging to delineate the integrity of spinal cord myelin. A subsequent in vivo PET imaging study of [F]PENDAS in rats with SCI showed promising pharmacokinetic results that justify further development of imaging markers for diagnosing myelin-related diseases. Additionally, [F]PENDAS could be valuable in determining the efficacy of therapies that are currently under development.

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http://dx.doi.org/10.1021/acs.jmedchem.8b01354DOI Listing

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