Multiple sclerosis (MS) is a common neurological disease that typically strikes people in their 20s. During MS, myelin, the insulating membrane that wraps around neurons, gets destroyed by an autoimmune process. Currently, MRI is the only tool to visualize the lesions in the brain and while it offers excellent resolution it lacks specificity. Therefore a molecular imaging tracer, such as for positron emission tomography (PET), would be greatly beneficial. Upon demyelination, K+ channels that are usually covered by the myelin sheath become exposed and leaky. The recently approved drug: 4-aminopyridine (4-AP, Ampyra) blocks these channels, which results in enhanced conduction and amelioration of the neurological symptoms. We hypothesized that this drug acts selectively on demyelinated axons and as such could be used as a tracer for the primary MS pathology.In this project, we designed and synthesized four fluorinated derivatives of 4-AP and tested their affinity against their target. Of these compounds, we found one that has very similar affinity as the original drug and better brain permeability and stability. We evaluated the distribution of the original drug and our lead compound in demyelinated brains from mice and found that these compounds do not bind to white matter tracks unless there is demyelination indicating the potential of these compounds as PET tracers for MS and other demyelinating diseases.

Fluorinated 4-aminopyridines as PET tracers for multiple sclerosis

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.