# PET Detection of CCR2 in Human Atherosclerosis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $764,984

## Abstract

A central modern tenet of atherosclerosis is that inflammation is a key driver of the process, and likely provides
at least a partial explanation for the excess CVD risk observed even after optimal treatment of traditional risk
factors. There is a critical unmet need for imaging tools that accurately risk stratify atherosclerotic patients based
on their inflammatory phenotype and identify those where a given therapy is indicated and then monitor its effect.
The monocyte chemoattractant protein-1 / C-C chemokine receptor type 2 (MCP-1/CCR2) axis is of particular
interest due to its central role in recruitment of pro-inflammatory monocytes which through their conversion of
pro-inflammatory macrophages are crucial for early atherosclerotic lesion formation and its progression. We
have developed a copper-64 radiolabeled extracellular loop 1 inverso (ECL1i) peptide PET radiotracer that
targets CCR2 ([64Cu]DOTA-ECL1i). We have shown this radiotracer provides sensitive and specific detection of
CCR2 receptor expression in a human monocytic cell line and ex-vivo human peripheral arterial atherosclerotic
plaque and tracks disease progression and treatment response in pre-clinical atherosclerotic models. Moreover,
we have initial human subject PET data to suggest [64Cu]DOTA-ECL1i noninvasively detects atherosclerotic
lesions.
Our objective is to perform the initial evaluation of the imaging performance of [64Cu]DOTA-ECL1i in humans
with peripheral carotid and femoral arterial atherosclerosis and obtain key biological information that is
foundational for the design of future studies to assess its capability for diagnosis, prognosis assignment and
evaluation of new therapies. To achieve this objective we will address, in parallel, the following Aims:
Aim 1. Evaluate the performance of [64Cu]DOTA-ECL1i PET/MR to detect CCR2+ monocytes and
macrophages in atherosclerotic plaques from patients undergoing carotid or femoral endarterectomy
(CEA and FEA): In Aim 1A we will evaluate the imaging characteristics of [64Cu]DOTA-ECL1i in normal
volunteers (Group 1) and in patients undergoing CEA (Group 2) or FEA (Group 3). Imaging performance will be
determined by correlation with standard MR readouts of plaque presence, size and stage and with ex-vivo tissue
measurements of CCR2 content/expression and inflammation determined by autoradiography and molecular
profiling assays. As an exploratory Aim we will assess the relationship between hematopoiesis and
atherosclerotic plaque progression. In Aim 1B we will determine the reproducibility of this approach in patients
with carotid and femoral artery atherosclerotic occlusive disease managed non-operatively.
Aim 2. Determine in ex-vivo human atherosclerotic CEA and FEA plaque samples the relationship
between [64Cu]DOTA-ECL1i binding, CCR2+ cellular expression, immune cell composition, cytokine
expression and plaque complexity. Atheromas are often heterogeneous with areas of variable intraplaque
calcification, hemorrhage, and...

## Key facts

- **NIH application ID:** 9905207
- **Project number:** 1R01HL150891-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Robert J. Gropler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $764,984
- **Award type:** 1
- **Project period:** 2020-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9905207

## Citation

> US National Institutes of Health, RePORTER application 9905207, PET Detection of CCR2 in Human Atherosclerosis (1R01HL150891-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9905207. Licensed CC0.

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