Central nervous system demyelination represents the pathological hallmark of multiple sclerosis (MS) and is thought to contribute to other neurological conditions including traumatic brain injury, stroke and Alzheimer’s disease. The ability to assess demyelination quickly and quantitatively is crucial for the diagnosis and treatment of these diseases. As current imaging approaches for demyelination rely on magnetic resonance imaging, which is neither quantitative nor specific for demyelination, Dr. Pedro Brugarolas set out to develop a PET tracer for demyelination. He described the development of a novel radioligand for brain imaging based on the FDA-approved drug for MS, 4-aminopyridine (4-AP). After demonstrating that C-14 labeled 4-AP localizes to demyelinated areas in mouse models of MS –presumably through binding to exposed potassium channels in demyelinated axons– he designed a fluorinated derivative of 4-AP compatible with with F-18 labeling and PET. Dr. Brugarolas then developed a novel radiochemical method to label this compound and performed PET/CT imaging in rats harboring demyelinated lesions. According to Dr. Pedro Brugarolas, this is the first example of a PET radioligand for potassium channels in the brain potentially opening a new window for looking at brain diseases.
Dr. Pedro Brugarolas is a radiochemist at the University of Chicago. He was the guest speaker of a lecture organized by the Gordon Center and his presentation was titled “[18F]3F4AP: a new PET tracer for imaging brain demyelination.”