Archive for February, 2018

Novel PET Imaging Tracer May Improve Monitoring of Multiple Sclerosis


[18F]3F4AP in the brain of healthy rhesus monkeys.

Multiple sclerosis is an immune-mediated neurological disease that affects around 400,000 people in the U.S. and 2.5 million worldwide. In the last few years, there has been a large effort by the academic community and pharmaceutical industry to develop drugs that can reverse demyelination and restore neurological function. One challenge for the translation of these therapies to humans is how to accurately measure their effects. Positron emission tomography (PET) has the potential to provide quantitative images of underlying biochemical processes such as demyelination.

In a recent paper* published by the journal Scientific Reports, Dr. Pedro Brugarolas and his colleagues describe the development and testing in animal models of a new PET tracer for demyelination. Their new tracer is based on the MS drug 4-aminopyridine (4AP, dalfampridine) which binds to potassium channels in demyelinated axons allowing the visualization of demyelinated lesions in animal models of MS noninvasively.

Dr. Brugarolas is an Assistant Professor of Radiology at Harvard Medical School and a Radiochemist at the MGH Gordon Center. His research at the Center focuses on developing novel small molecule PET tracers labeled with fluorine-18 and carbon-11

*Brugarolas, P., Sánchez-Rodríguez, J. E., Tsai, H.-M., Basuli, F., Cheng, S.-H., Zhang, X., et al. (2018). Development of a PET radioligand for potassium channels to image CNS demyelination. Scientific Reports, 8 (1), 607.

Study Reveals Association between Aβ, Tau, Circuitry and Cognition


A new study published in Nature Neuroscience revealed an association between Aβ, Tau, Circuitry and Cognition. The study was conducted by Dr. Heidi Jacobs, instructor at MGH Gordon Center and a Marie Curie Fellow, and Dr. Keith Johnson, leader of the Aging NeuroImaging Program at the MGH Gordon Center, and the Harvard Aging Brain Study.

Using longitudinal multimodal imaging data collected in healthy older individuals, they provided in vivo evidence in humans that amyloid deposition facilitates tau spread along structurally connected pathways and this combination of events is associated with memory decline.

Imaging modalities included positron-emission tomography (PET) and magnetic resonance imaging (MRI). PET imaging was performed using the tracer flortaucipir (FTP), which binds to tau pathology, and the tracer Pittsburg compound-B (PiB), which indicates amyloid deposition. MR imaging was performed using T1-weighted images to measure hippocampal volume, and diffusion tensor imaging (DTI) was used to measure tract diffusivity.

The results of this study showed that hippocampal volume at baseline, a proxy for neurodegenerative processes including tau pathology, predict changes in diffusivity in a tract innervating the hippocampus, the hippocampal cingulum bundle (HCB), and not in a control tract, the uncinate fasciculus (UF).

These diffusivity changes in the hippocampal cingulum bundle were in turn associated with accumulation of tau pathology outside the medial temporal lobe, in the connected posterior cingulate cortex (PCC), in individuals with elevated levels of amyloid pathology. Finally, the combination of these diffusivity changes in the hippocampal cingulum bundle and higher levels of posterior cingulate cortex tau were associated with memory decline in individuals with elevated levels of amyloid pathology. These findings suggests that amyloid plays a crucial role in driving neurodegenerative processes and cognitive decline, and that monitoring spread of tau pathology will be important in clinical trials focused on removing amyloid plaques in the earliest stages of the diseases.

A detailed summary of this study is featured in AlzForum.

Associations between tract diffusivity, tau accumulation in the PCC, amyloid pathology and memory performance

Jacobs HI, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, Papp KV, Rentz DM, Sperling RA, Johnson KA. "Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals" Nat Neurosci. 2018 Feb 5;

Research Agreement Signed with Cerveau Technologies


Cerveau Technologies Inc. signed an agreement with the MGH Gordon Center to support multiple projects over the next several years. These research projects are for studies of an early stage imaging agent (MK-6240) to be used in Positron Emission Tomography (PET) scans for assessing the status and progression of neurofibrillary tangles (NFTs) in the brain. NFTs made up of aggregated tau protein are a hallmark of several neurodegenerative diseases, including Alzheimer’s disease.

As part of the agreement, Cerveau will contract with the Gordon Center for Medical Imaging, a research center and PET imaging facility within MGH, to manufacture and supply the [18F]MK-6240 needed for initiatives in the greater Boston area. “We are glad to be part of the effort to make Tau PET available to the New England research community as it is becoming a tool of choice for in vivo assessment of tau pathology in many brain disorders,” said Dr. Georges El Fakhri, Director of the MGH Gordon Center.

According to Dr. Keith Johnson, leader of the Aging NeuroImaging Program at the MGH Gordon Center, and the Harvard Aging Brain Study, “the ability to detect tau brain pathology in living humans is a major medical breakthrough. The value of this novel technology has already been demonstrated to improve the likelihood we can develop treatments for Alzheimer’s disease. In addition, however, brain tau deposition is a major player in chronic traumatic encephalopathy, fronto-temporal dementia, and several forms of Parkinsonism. This means that successful research program initiatives for novel radio-pharmaceuticals such as MK6240 are an important advance toward refinement and optimization of tau PET, which is the rapidly developing biomarker technology aimed at tracking tau pathology in a variety of brain disorders.”

“Cerveau welcomes this opportunity to work with the MGH researchers, who have a very successful history of leadership in this field to understand the application of MK-6240 and how it may benefit patients with brain diseases. The collaboration with the Gordon Center at MGH will also provide access to our pharmaceutical partners in support of various therapy trials and support our global production network in Europe, Canada, Japan, China, Singapore, Australia and the United States as well facilitate novel research at MGH in the pursuit of evaluating potential preventive treatment options for Alzheimer’s disease,” said Rick Hiatt, President and CEO of Cerveau Technologies, Inc.

Read more:

Brain PET scan

Keith Johnson Named 2017 Clarivate Analytics Highly Cited Researcher


Dr. Keith Johnson has been named to the 2017 “Highly Cited Researchers” list from Clarivate Analytics.

The list recognized 3,538 highly cited researchers in 21 fields of the sciences and social sciences. These researchers have distinguished themselves by publishing a high number of papers that rank in the top one percent most-cited in their respective fields internationally over a recent 11-year period.

Keith Johnson's research focuses on developing preventive therapies and treatment of Alzheimer's disease. His lab at the MGH Gordon Center is investigating imaging agents that can detect tau deposits in the brain related to cognitive impairment.

Keith Johnson , MD, PhD