Can [18F]3F4AP Detect Brain Demyelination? Evaluation of Novel PET Tracer in Nonhuman Primates and Humans

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Principal Investigator: Pedro  Brugarolas
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2024
Award: $351,929
Funding agency: National Institute of Neurological Disorders and Stroke

Project Summary
 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.

Terms: <4-Aminopyridine><4-Pyridinamine><AD dementia><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Animal Model><Animal Models and Related Studies><Apoplexy><Architecture><Area><Axon><Binding><Biochemical><Blood - brain barrier anatomy><Blood Sample><Blood specimen><Blood-Brain Barrier><Brain><Brain Ischemia><Brain Nervous System><Brain Trauma><Brain Vascular Accident><Brain imaging><CNS Nervous System><Cell Communication and Signaling><Cell Signaling><Central Nervous System><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Clinical><Clinical Research><Clinical Study><Cognitive Manifestations><Cognitive Symptoms><Common Rat Strains><Complement><Complement Proteins><Craniotomy><Data><Demyelinating Diseases><Demyelinating Disorders><Demyelinations><Diagnosis><Disease><Disorder><Disseminated Sclerosis><Drug usage><Drugs><Encephalon><Engineering / Architecture><Evaluation><FDA approved><Fiber><Future><Genetic><Goals><Hemato-Encephalic Barrier><Histologic><Histologically><Human><Image><Imaging Device><Imaging Instrument><Imaging Tool><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Inflammation><Injury><Intermediary Metabolism><Intracellular Communication and Signaling><Ischemia><Ischemic Encephalopathy><K channel><Kinetics><Lesion><M mulatta><M. mulatta><MR Imaging><MR Tomography><MRI><MRIs><Macaca mulatta><Magnetic Resonance Imaging><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medication><Metabolic><Metabolic Processes><Metabolism><Methods><Minor><Modeling><Modern Man><Molecular Interaction><Monitor><Monkeys><Motor><Multiple Sclerosis><Myelin><Myelin Sheath><Myelin Water Imaging><NMR Imaging><NMR Tomography><Nerve Cells><Nerve Unit><Neural Cell><Neuraxis><Neurobehavioral Manifestations><Neurobehavioral Signs and Symptoms><Neurocyte><Neurons><Nuclear Magnetic Resonance Imaging><Nutrient><PET><PET Scan><PET imaging><PETSCAN><PETT><Pathologic Processes><Pathological Processes><Penetration><Performance><Pharmaceutical Preparations><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Potassium Channel><Potassium Ion Channels><Primary Senile Degenerative Dementia><Primates><Primates Mammals><Procedures><Process><Property><Pymadine><Rad.-PET><Rat><Rats Mammals><Rattus><Rhesus Macaque><Rhesus Monkey><Rodent><Rodent Model><Rodentia><Rodents Mammals><Role><Scanning><Sensory><Severity of illness><Signal Transduction><Signal Transduction Systems><Signaling><Speed><Stroke><Target Populations><Testing><Time><Tracer><Traumatic Brain Injury><Voltage-Gated K+ Channels><Voltage-Gated Potassium Channel><Walking><Zeugmatography><biological signal transduction><bloodbrain barrier><brain attack><brain injury and spinal cord injury><brain visualization><brain/spinal cord injury><cerebral vascular accident><cerebrovascular accident><complementation><de-myelinating diseases><de-myelinating disorders><demyelinate><demyelinating conditions><demyelination diseases><demyelination disorders><design><designing><develop therapy><disease severity><drug use><drug/agent><experiment><experimental research><experimental study><experiments><first in man><first-in-human><imaging><imaging properties><information gathering><injured><injuries><insular sclerosis><intervention development><kinetic model><leukodystrophy><micro PET><micro positron emission tomography><microPET><model of animal><natural aging><neurobehavioral symptom><neuronal><non-human primate><nonhuman primate><normal aging><normative aging><novel><overexpress><overexpression><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><primary degenerative dementia><quantitative imaging><radiolabel><radiolabels><radioligand><radiotracer><re-myelinate><re-myelination><remyelinate><remyelination><senile dementia of the Alzheimer type><skull incision><social role><spinal cord and brain injury><stroked><strokes><therapy development><traumatic brain damage><treatment development>