# Delaware INBRE

> **NIH NIH P20** · UNIVERSITY OF DELAWARE · 2024 · $208,400

## Abstract

PROJECT SUMMARY/ABSTRACT
The glymphatic-lymphatic system plays an essential role in immune surveillance and clearance of metabolic
waste. Dysfunction of the system is closely associated with neurodegenerative disorders. While the existence of
brain lymphatic vessels (mLVs) was proposed more than 200 years ago, it was only reliably confirmed with solid
experimental evidence in 2015. Fluorescent imaging and gadolinium-based contrast agents (GBCA) have since
been used to probe the brain’s glymphatic-lymphatic system in rodents and nonhuman primates. However,
current strategies for imaging the glymphatic-lymphatic system have several limitations that preclude their use
for in vivo imaging and application in the clinical setting. The vascular endothelial growth factor receptor 3
(VEGFR3), a tyrosine kinase receptor, is expressed exclusively by the lymphatic endothelium. Deletion of
VEGFR3 in mouse pups led to a nearly complete lack of mLVs and compromised waste clearance. In addition,
VEGFR3 may also contribute to clearing parenchymal wastes in the glymphatic system through the bidirectional
water channel aquaporin-4. Positron emission tomography (PET) is a sensitive and noninvasive imaging
modality (nM to pM) used to clinically assess metabolism, enzymes, receptors, and transporters at the molecular
level. In response to the Notice of Special Interest (NOSI): Availability of Administrative Supplements to INBRE
Awards to Fund Research Collaborations (NOT-GM-22-001), we assembled a team with the Delaware State
University (DSU). We hypothesize that fluorine-18 labeled VEGFR3-specific radiotracers can be used for real-
time PET imaging of the whole brain’s glymphatic-lymphatic system. To test our hypothesis, we propose two
aims. In Aim 1, the Co-Project Leader from DSU will use their knowledge of biomolecules and biochemical
pathways to identify a systematic biomarker relevant to whole-brain waste clearance and protein aggregation in
neurodegenerative disorders. In Aim 2, the Co-Project Leader from Nemours will design and synthesize new
imaging agents targeting the biomarkers with high binding affinity and selectivity and optimize the imaging agents
in terms of stability, BBB penetration, easy radiolabeling, and metabolic profile. The innovative proposal and
interdisciplinary collaboration will lay the foundation for further real-time live animal imaging in neurodegenerative
disorders and clinical translation for new diagnostics and therapeutics development. The pilot project will lead to
the discovery of new biomarkers in the CNS, improved imaging techniques, and ultimately, better diagnosis and
treatment of CNS diseases. Furthermore, preliminary data from this INBRE supplement will inform an R01
application by targeting PAR-23-165.

## Key facts

- **NIH application ID:** 11020173
- **Project number:** 3P20GM103446-23S6
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** MELINDA K DUNCAN
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $208,400
- **Award type:** 3
- **Project period:** 2001-09-30 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11020173

## Citation

> US National Institutes of Health, RePORTER application 11020173, Delaware INBRE (3P20GM103446-23S6). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11020173. Licensed CC0.

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