Tracer molecule may improve imaging tests for brain injury

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Researchers have validated a new radiolabelled molecule that can be used with imaging tests to accurately identify and characterize brain injuries. The team, led by investigators from Massachusetts General Hospital (MGH), recently received approval from the U.S. Food and Drug Administration (FDA) to initiate an initial human study using this strategy.

As described in the Journal of Cerebral Blood Flow & Metabolism, the new type of tracer is called [18F]3F4AP is designed to bind to potassium channels and is radiolabelled so that it can be visualized by positron emission tomography (PET). Potassium channels in the neurons of the brain are exposed when the neurons become demyelinated or lose their protective layer (called myelin), which occurs in a variety of neurodegenerative conditions.

“As the expression and accessibility of potassium channels increases in demyelination, this tracer holds great promise for imaging multiple sclerosis and other diseases such as traumatic brain and spinal cord injury, stroke and Alzheimer’s disease,” said co-senior author Pedro Brugarolas, Ph.D. , an investigator at MGH’s Gordon Center for Medical Imaging and an assistant professor in the Radiology Department at Harvard Medical School.

When testing monkeys, [18F]3F4AP demonstrated excellent brain imaging properties, including high brain penetration, quick washout or clearance, and excellent reproducibility when tested multiple times, researchers say. In addition, “the tracer showed unusually high resistance to metabolic degradation and minimal binding to blood proteins – properties that are difficult to obtain and of great use for PET imaging,” said senior author Nicolas Guehl, Ph. D., a researcher in the Department of Radiology at MGH and a lecturer in Radiology at Harvard Medical School (HMS).

The tracer also produced a high level signal in the right frontal cortex of a monkey that the researchers later learned had suffered a mild brain injury several years before it was transmitted. “The tracer detected the brain lesion better than other PET tracers commonly used for brain imaging and better than magnetic resonance imaging, the standard imaging modality used to detect demyelination,” said co-senior author Marc Normandin, Ph .D., Associate Director of the Gordon Center for Medical Imaging at MGH and Assistant Professor at HMS.

The team is now ready to test the work on patients who have been approved by the FDA. “There are many tracers that have been developed and tested on animals that never make it to humans. This is a major achievement,” said Daniel Yokell, PharmD, associate director of radiopharmaceuticals and regulatory affairs for the Gordon PET Core at MGH, who does the FDA has prepared Investigational New Drug application that has been approved.

Human testing will likely begin immediately. “We are pleased that the MGH Gordon PET Core is the first production site [18F]3F4AP for clinical investigations and to study its role in many promising applications, “said co-author Georges El Fakhri, Ph.D., director of MGH’s Gordon Center for Medical Imaging and professor of radiology with Nathaniel and Diana Alpert at HMS .

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More information:
Nicolas J. Guehl et al., Evaluation of the Potassium Channel Tracer [8F]3F4AP in rhesus monkeys, Journal of Cerebral Blood Flow & Metabolism (2020). DOI: 10.1177 / 0271678X20963404 Provided by Massachusetts General Hospital

Quote: Tracer Molecule May Improve Brain Injury Imaging Tests (2020, October 22), accessed from on October 23, 2020

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