PET Scans May Help Image Multiple Sclerosis-Related Damage

There is currently no direct way to image demyelination related to multiple sclerosis (MS). Presently, physicians rely on MRI imaging; however, this technique is unable to differentiate between demyelination and inflammation, which are both common among patients with MS.

A recent study published by Scientific Reports suggests that positron emission tomography (PET) scans may allow researchers to assess myelin damage in a minimally-invasive way.

Investigational PET scans use a radioactive molecule that targets voltage-gated potassium channels, which are proteins found on demyelinated axons, according to the authors.

The study results suggest that the detection of this molecule can provide qualitative information about biochemical processes, according to the authors.

"In healthy myelinated neurons, potassium channels are usually buried underneath the myelin sheath," said study author Brian Popko, PhD. "When there is loss of myelin, these channels become exposed. They migrate throughout the demyelinated segment and their levels increase."

Exposed neurons leak intracellular potassium, which can cause neurological symptoms seen in MS, according to the study. To address this issue, the research team developed a PET tracer that can target potassium channels.

The authors used 4-aminopyridine (alfampridine), an existing MS drug that binds to exposed potassium channels. The authors said that this treatment partially restores nerve conduction and reduces neurological symptoms. In mouse models of MS, 4-aminopyridine accumulated in demyelinated areas of the central nervous system.

In the new study, the authors labeled 3-flouro-4-aminopyridine (3F4AP) with fluorine-18, which can be detected by PET scans.

"We were able to show, in rats, that the tracer accumulated to a higher degree in demyelinated areas than in control areas," Dr Popko said.

These results suggest that PET scans may be effective at quantifying MS-related damage.

"All existing PET tracers used for imaging demyelination bind to myelin and, consequently, demyelinated lesions show as decreases in signal, which can be problematic for imaging small lesions," said first author Pedro Brugarolas, PhD. "3F4AP is the first tracer whose signal increases with demyelination, potentially solving some of the problems of its predecessors."

The authors further tested this approach in healthy monkeys and confirmed that radiolabeled 3F4AP enters the brains of primates and accumulates where there is little myelin, according to the study.

"We think that this PET approach can provide complementary information to MRI which can help us follow MS lesions over time," Dr Popko said. "It has the potential to track responses to remyelinating therapies, an unmet need. This approach should also help determine how much disruption of the myelin sheath contributes to other central nervous system disorders."

The authors hypothesize that these PET scans could be beneficial for imaging leukodystrophies, traumatic brain injury, spinal cord injury, and other conditions that are not generally associated with demyelination, including brain ischemia, psychiatric disorders, and neurodegenerative diseases.

"A tracer to monitor changes in something as ubiquitous as potassium channels could have applications for other diseases where these channels are involved," Dr Brugarolas concluded.