# PET Imaging Biomarkers to Predict Cardiac Remodeling and Functional Decline in Cardiotoxicity Arising from Chemotherapy

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $237,724

## Abstract

Successful treatment of cancer is hampered by the attendant risk of cardiotoxicity, manifesting as
cardiomyopathy, left ventricle systolic dysfunction and, in some cases, heart failure. This risk can be mitigated if
the damage to the heart is detected before it becomes irreversible. Current assessment of cardiotoxicity relies
upon functional measures that may not detect early myocardial damage with sensitivity or predict subsequent
declines in function. New biomarkers and metrics are therefore needed to identify at-risk patients prior to therapy
and to detect the onset of cardiotoxicity during or after chemotherapy. The contribution of multiple processes to
progression to cardiomyopathy and heart failure, including inflammation, fibrosis, and cardiac sympathetic
neuron dysfunction, that can be measured by sensitive, high resolution, and non-invasive imaging techniques
such as PET, are proposed herein as a new approach to diagnosing and monitoring cardiotoxicity.
Norepinephrine is the major transmitter of the sympathetic neuron system, making the norepinephrine
transporter (NET) an attractive marker of sympathetic neuron function. Fibroblast activation protein alpha
(FAP) is a marker of activated fibroblasts, which are thought to effect fibrosis during cardiac remodeling. Finally,
Translocator Protein 18 kDa (TSPO) is a mitochondrial protein whose expression in the myocardium is
sensitive to inflammation and mitochondrial dysfunction. The aim of this project is to evaluate the predictive
and/or diagnostic value of these biomarkers for detection of cancer therapy-induced cardiotoxicity.
 We propose to use three PET radioligands that are already in clinical use for other indications to image
NET activation ([18F]]MFBG), FAP expression ([68Ga]FAPI-02), and TSPO expression ([18F]DPA-714) in a
preclinical model of doxorubicin-induced cardiotoxicity. We hypothesize that [18F]MFBG signal will decrease and
[68Ga]FAPI-02 and [18F]DPA-714 will increase in the myocardium following chemotherapy. To test our
hypothesis, we will induce chronic cardiotoxicity in C57BL/6 mice by administration of doxorubicin (cumulative
dose of 24 mg/kg), and perform weekly dynamic μPET/CT imaging for 6 weeks. The images will be analyzed to
determine maximum standardized uptake (SUVmax) and plot time-activity curves (TACs). Temporal changes in
tracer uptake will be compared to concurrent measurements of cardiac function by echocardiography and
morphological features of cardiotoxicity, such as hypertrophy, inflammation, and fibrosis, by
immunohistochemistry. The compounds will be ranked in terms of their predictive and/or diagnostic value.
We will attempt to distinguish between markers of early- and late-onset progressive cardiomyopathy,
and will put forward the leading candidates for clinical imaging of chemotherapy-induced cardiotoxicity.
In selecting radioligands that are already in clinical use for other indications, we are confident that
successful validation of these imaging...

## Key facts

- **NIH application ID:** 9877339
- **Project number:** 1R21CA246409-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** John W Babich
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,724
- **Award type:** 1
- **Project period:** 2019-12-12 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877339

## Citation

> US National Institutes of Health, RePORTER application 9877339, PET Imaging Biomarkers to Predict Cardiac Remodeling and Functional Decline in Cardiotoxicity Arising from Chemotherapy (1R21CA246409-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9877339. Licensed CC0.

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