# Targeted Molecular Probes for Atherosclerosis Imaging and Therapy

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2020 · $730,357

## Abstract

Summary
Atherosclerosis is a progressive disease characterized by the development of lipid-rich, inflammatory plaque
lesions within vessel walls. It is the underlying basis of cardiovascular diseases including myocardial infarction,
stroke, and peripheral arterial disease. However, the ability to reliably detect the vulnerable plaque and identify
high-risk patients has been a challenge. Further, there is no imaging agent to detect the eroded plaques, a less-
known subtype accounting for one third of clinical events. Chemokines and chemokine receptors play important
roles in atherosclerosis from initialization to clinical event by directing leukocyte trafficking. We have developed
chemokine receptor targeted positron emission tomography (PET) imaging agents and demonstrated the
specific detection of monocyte trafficking in vivo and track plaque progression and regression. To further
explore the potential of these imaging agents for translation, we would like to propose a research program to
develop novel PET tracers with potential to identify vulnerable plaques, detect plaque erosion, and more
importantly to track the treatment response to improve patient outcome. Specifically, we will firstly optimize the
design and synthesis of a portfolio of PET tracers targeting plaque-relevant targets including CCR2, CCR5,
CXCR3, CD44, and TLR2 to improve the radiolabeling and scale-up capability through controlled
radiochemistry and bioconjugate chemistry, and binding affinities by varying the charge, surface chemistry and
polymer coating materials. Secondly, we will perform in vivo biodistribution studies and PET imaging in
atherosclerosis progression/regression and complication mouse models, as well as rabbit atherosclerosis
models to assess the imaging specificity, sensitivity, and capability to track the immune cells in vivo and
correlation with targets expression and plaque characteristics. Thirdly, we will assess the capability of
developed imaging probes to determine treatment response for improved outcome and binding to ex vivo
human plaque tissue for future translation. We propose to submit multiple exploratory investigational new drug
application to FDA and have two PET tracers ready for human trials at the end of grant period. The
establishment of this research program will not only promote the development of targeted PET tracers for
atherosclerosis translational imaging, but also broader applications in other diseases within the NHLBI mission.

## Key facts

- **NIH application ID:** 9874002
- **Project number:** 5R35HL145212-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Yongjian Liu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $730,357
- **Award type:** 5
- **Project period:** 2019-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874002

## Citation

> US National Institutes of Health, RePORTER application 9874002, Targeted Molecular Probes for Atherosclerosis Imaging and Therapy (5R35HL145212-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9874002. Licensed CC0.

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