Demyelination represents the hallmark of multiple sclerosis (MS) and is also present in other diseases including brain ischemia, traumatic brain injury and even Alzheimer?s disease. Currently, demyelinating diseases are primarily imaged using MRI. Even though MRI is highly sensitive to demyelination, it is not quantitative and it cannot distinguish demyelination from other potentially coexisiting pathological processes such as inflammation or axonal loss. Positron Emission Tomography (PET) can provide quantitative and biochemically specific information to complement MRI. We recently developed a PET radiotracer for demyelination based on the FDA-approved drug for MS 4- aminopyridine (4AP) called [18F]3F4AP. We showed that this tracer be used to detect demyelination in rodent models of MS and that it has good properties for imaging the brain in monkeys. In this project, we seek to investigate the potential of this tracer for imaging demyelination in a model of traumatic brain injury and to validate it in nonhuman primates and humans. The information gathered here will be crucial for the design and interpretation of future human studies. Once validated, this tracer and could contribute to better monitoring of demyelinating diseases and to the development of therapies to reverse demyelination.

Public Health Relevance

We recently developed a PET radioligand for K+ channels in the brain that can detect demyelinated lesions in animal models non-invasively. Here, we propose to examine this tracer in rodents, monkeys and humans to further understand the applications and performance of this tracer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS114066-02
Application #
10069413
Study Section
Emerging Imaging Technologies in Neuroscience Study Section (EITN)
Program Officer
Utz, Ursula
Project Start
2019-12-15
Project End
2024-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114