# Targeting Lymphatic Vessels for Ligand Directed Imaging

> **NIH NIH R01** · RBHS -CANCER INSTITUTE OF NEW JERSEY · 2020 · $363,713

## Abstract

ABSTRACT
 . In particular, the
The phenomenon of molecular changes to the lymphatic endothelial cells and the biological role(s) of the
lymphatic vasculature in the metastatic cascade of human cancer are not entirely understood
syndrome of in-transit melanoma is a fascinating clinical example of disease presentation in search of a
pathophysiological basis. In our recent paper, Ligand-directed targeting of lymphatic vessels uncovers
mechanistic insights in melanoma metastasis (Christianson et al. PNAS, 2015), we performed ex vivo
combinatorial screens using random peptide phage libraries of draining lymphatic channels removed directly
from patients during melanoma excision surgeries. We discovered a functional ligand-receptor system by
selecting, isolating, and validating a new homophilic protein-protein interaction between malignant melanoma
cells and lymphatic endothelial cells. This unique and previously unrecognized finding provides the foundation
for the development and optimization of a new platform for ligand-directed imaging of the lymphatic system.
Here, we propose to interrogate previously identified peptide ligands that bind to the surface of the lymphatic
endothelium during disease progression to develop a novel, ligand-directed, non-invasive in vivo lymphatic
imaging platform. Specifically, our goals are to: (1) Use innovative chem- and bio-informatics data mining
systems to define the ontology of enriched lymphatic vessel homing peptides, (2) Investigate the binding
properties of selected peptide ligands and their corresponding receptors in vitro, and (3) Develop and
implement targeted imaging systems to study the lymphatic endothelium. Peptides that home to PPP2R1A, a
new powerful lymphatic marker, will be prioritized. Our long-term goal, subsequent to the completion of the
work proposed here, is to discover new lymphatic biomarkers associated with disease progression and
generate a panel of ligand-based imaging agents that specifically target the surface of the lymphatic
endothelium for prognostic and diagnostic translational applications. We anticipate that the newly characterized
lymphatic molecular addresses and validated, corresponding ligands and antibodies will be of great value for
the development of targeted agents, establishing for the first time, a platform for non-invasive imaging of the
lymphatic system, and, in the future, contribute to our understanding of the role by the lymphatic vasculature in
human disease.

## Key facts

- **NIH application ID:** 9827550
- **Project number:** 5R01CA204517-05
- **Recipient organization:** RBHS -CANCER INSTITUTE OF NEW JERSEY
- **Principal Investigator:** WADIH ARAP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,713
- **Award type:** 5
- **Project period:** 2016-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9827550

## Citation

> US National Institutes of Health, RePORTER application 9827550, Targeting Lymphatic Vessels for Ligand Directed Imaging (5R01CA204517-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9827550. Licensed CC0.

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