# FAP PET identifies earlycardiac molecular changesinduced by doxorubicin chemotherapy

## TL;DR

A PET imaging technique using a specific probe can detect early heart damage caused by doxorubicin chemotherapy before function declines.

## Contribution

FAP PET imaging is shown to detect early cardiac changes from doxorubicin before functional decline in mice.

## Key findings

- Elevated FAP PET signal was observed in mice by 2 weeks after doxorubicin treatment.
- FAP PET signal correlated with FAP expression and cardiac remodeling indicators.
- Other PET tracers did not show differences between treated and control mice.

## Abstract

Anthracycline chemotherapy, widely used in cancer treatment, poses a significant risk of cardiotoxicity that results in functional decline. Current diagnostic methods poorly predict cardiotoxicity because they do not detect early damage that precedes dysfunction. Positron emission tomography (PET) is well suited to address this need when coupled with suitable imaging biomarkers. We used PET to evaluate cardiac molecular changes in male C57BL/6J mice exposed to doxorubicin (DOX). These mice initially developed cardiac atrophy, experienced functional deficits within 10 weeks of treatment, and developed cardiac fibrosis by 16 weeks. Elevated cardiac uptake of [68Ga]Ga-FAPI-04, a PET tracer targeting fibroblast activation protein α (FAP), was evident by 2 weeks and preceded the onset of functional deficits. Cardiac PET signal correlated with FAP expression and activity as well as other canonical indicators of cardiac remodeling. By contrast, cardiac uptake of [18F]DPA-714 and [18F]MFBG, which target translocator protein 18 kDa and the norepinephrine transporter, respectively, did not differ between the DOX animals and their controls. These findings identify FAP as an early imaging biomarker for DOX-induced cardiac remodeling in males and support the use of FAP PET imaging to detect some cancer patients at risk for treatment-related myocardial damage before cardiac function declines.

Positron emission tomography using a probe that targets fibroblast activation protein detects incipient cardiotoxicity induced by doxorubicin before overt declines in heart function