# PET Imaging of MMP Activation in AAA: First in-Human Evaluation

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $640,579

## Abstract

Abstract
 Abdominal aortic aneurysms (AAA) are responsible for 10,000 documented deaths every year in the
US. While most aneurysms are asymptomatic, highly lethal complications, rupture and dissection do occur in a
subset of patients. Aneurysm diameter is the best-known predictor of its propensity to rupture, and
accordingly, aneurysm repair is recommended for large, or symptomatic AAA. However, many ruptures
occur in smaller aneurysms that do not meet the criteria for repair; and conversely, some larger aneurysms
do not rupture. AAA treatment remains limited to surgical or endovascular repair, as several promising medical
therapies have failed in clinical studies. As such, novel tools (e.g., molecular imaging) are needed to better risk
stratify patients, develop effective medical therapies, and monitor therapeutic effectiveness. Matrix
metalloproteinases (MMP) activation promotes vascular remodeling in AAA, in part through degradation of
elastin and other matrix proteins. Our previous studies have established the feasibility of MMP-targeted
imaging to detect vascular remodeling by micro single photon emission computed tomography (SPECT)/CT in
murine models of aneurysm. However, a number of limitations of the SPECT tracer and technology precluded
clinical translation for vascular imaging. To address these limitations, we developed a novel family of MMP-
targeted tracers (RYM) with improved pharmacokinetics, including a first in the class positron emission
tomography (PET) tracer, 64Cu-RYM2. Here, we seek to further develop, evaluate, and clinically translate
64Cu-RYM2 for first in human imaging studies in AAA, hypothesizing that MMP PET/CT imaging with 64Cu-
RYM2 can detect AAA MMP activity. Our specific aims are to evaluate 64Cu-RYM2 binding to human AAA
tissue; address 64Cu-RYM2 pharmacokinetics and imaging performance in murine AAA in relation to tissue
MMP activity; and translate 64Cu-RYM2 for human AAA imaging. Leveraging the resources and
complementary expertise of the PIs and co-investigators at Yale School of Medicine and Washington
University, including an NIBIB-funded P41- center at Washington University, these studies will establish the
potential of 64Cu-RYM2 to quantify MMP activation in human AAA, and set the stage for a multi-center trial of
MMP PET/CT imaging for AAA risk stratification.

## Key facts

- **NIH application ID:** 10617801
- **Project number:** 5R01AG065917-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Robert J. Gropler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $640,579
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617801

## Citation

> US National Institutes of Health, RePORTER application 10617801, PET Imaging of MMP Activation in AAA: First in-Human Evaluation (5R01AG065917-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10617801. Licensed CC0.

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