# Non invasive in vivo imaging of pathological fibrin deposition in the human brain

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $210,000

## Abstract

Abstract:
 A growing body of evidence indicates that fibrinogen and the pathways that control the
formation and degradation of fibrin could represent early triggers that contribute to the
initiation of neuroinflammation and the promotion of neurodegeneration in a variety of
neurological disorders including traumatic brain injury, Alzheimer disease, and multiple
sclerosis (MS), a neuroinflammatory and neurodegenerative disorder of the CNS and the
second most common cause of neurological disability (after trauma) in young adults in
Western countries. Fibrinogen is a 340 kDa glycoprotein generally considered a good
surrogate marker of blood brain barrier (BBB) disruption because of its abundance,
restriction to the intravascular compartment and lack of expression in the healthy CNS.
Upon activation of the coagulation cascade, fibrinogen is converted into insoluble fibrin
by thrombin. Previous studies have demonstrated that fibrin deposition is a prominent
pathological feature of MS and is present throughout the course of the disease.
Neuropathological examinations of ex vivo progressive MS brains have provided
evidence that fibrin deposition in the disease is not only confined to the white matter
(WM), but it can be also extensive and frequent in the MS cortex, where it correlates with
neuronal loss. In MS, cortical demyelination and neurodegeneration represent main
components of disease pathology, particularly in progressive stages, and key substrates
of irreversible neurological disability.
 Here, we propose to combine 7-Tesla ultra-high resolution magnetic resonance
imaging (MRI), which shows increased sensitivity relative to lower field MRI to cortical
lesion pathology, with molecular positron emission tomography using 64Cu-FBP8, a
novel molecular imaging probe developed at Massachusetts General Hospital, which
selectively binds to fibrin, to image and quantify in vivo pathological deposition of fibrin in
the brain of people with progressive MS, with a specific focus on the cortex and its
association to local lesions and tissue loss. Safety data demonstrate that 64Cu-FBP8
shows nanomolar affinity for fibrin, high selectivity for fibrin over plasma proteins, is
metabolically stable, and is rapidly renally excreted.The ability to track in vivo fibrin
deposition in MS will be crucial for better understanding the pathological events that lead
to neuroinflammation and cortical damage in MS, and for developing novel biomarkers
for monitoring early events that lead to neuroinflammation in MS.

## Key facts

- **NIH application ID:** 10428755
- **Project number:** 1R21NS126737-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Caterina Mainero
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $210,000
- **Award type:** 1
- **Project period:** 2022-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428755

## Citation

> US National Institutes of Health, RePORTER application 10428755, Non invasive in vivo imaging of pathological fibrin deposition in the human brain (1R21NS126737-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10428755. Licensed CC0.

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