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Molecular imaging of fibroblast activity in pressure overload heart failure using [68 Ga]Ga-FAPI-04 PET/CT

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Abstract

Purpose

We aimed to evaluate whether [68 Ga]Ga-FAPI-04 PET/CT could characterize the early stages of cardiac fibrosis in pressure overload heart failure.

Methods

Sprague–Dawley rats underwent abdominal aortic constriction (AAC) (n = 12) and sham surgery (n = 10). All rats were scanned with [68 Ga]Ga-FAPI-04 PET/CT at 2, 4, and 8 weeks after surgery. The expression of fibroblast activation protein (FAP) in the myocardium was detected by immunohistochemistry. [68 Ga]Ga-FAPI-04 PET signal and FAP expression were compared between two groups.

Results

Compared with the sham group, the AAC group presented with decreased ejection fraction (EF) and fractional shortening (FS) and increased left ventricular internal dimensions in diastole (LVIDd) and systole (LVIDs) at 4 and 8 weeks (all p < 0.01). The AAC group showed higher [68 Ga]Ga-FAPI-04 accumulation in the heart than the sham group at 2, 4, and 8 weeks, and FAPI increased significantly from 2 to 8 weeks (all p < 0.001). Immunohistochemistry confirmed the higher density of the FAP+ area in the AAC group. The intensity of the [68 Ga]Ga-FAPI-04 correlated with the density of the FAP+ area (p < 0.001). The expression of the [68 Ga]Ga-FAPI-04 at 4 weeks correlated with the deterioration of cardiac function at 8 weeks (EF: R =  − 0.87; FS: R =  − 0.72; LVIDd: R = 0.77; LVIDs: R = 0.79; all p < 0.001). The AAC group also showed an increased [68 Ga]Ga-FAPI-04 signal in the liver, peaking at 4 weeks and then declining. Cardiac and liver PET signals correlated at 4 weeks in the AAC group (R = 0.69, p = 0.0010), suggesting an early fibrotic link between organs. A combination of the [68 Ga]Ga-FAPI-04 intensity in the heart and liver at 4 weeks better predicted the deterioration of cardiac function at 8 weeks.

Conclusions

The activated fibroblasts in the heart and liver after pressure overload can be monitored by [68 Ga]Ga-FAPI-04 PET/CT, which reveals an early fibrotic link in cardio-liver interactions and could better predict nonischemic heart failure prognosis.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Funding

This work was financially supported by the “234 Discipline Climbing Plan” of the First Affiliated Hospital of Naval Medical University (2019YPT002, 2020YPT002), and the Shanghai Science and Technology Innovation Action Plan “Science and Technology Support Project in Biomedical Science” (21S11906000).

Author information

Author notes

  1. Drs Guokun Wang, Qinqin Yang, and Shengyong Wu contributed equally to this work and are co-first authors.

  2. Drs Chao Cheng and Suxuan Liu contributed equally to this work and are co-corresponding authors.

Authors and Affiliations

  1. Department of Cardiovascular Surgery, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, Shanghai, China

    Guokun Wang

  2. Department of Nuclear Medicine, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, 168 Changhai Road, Shanghai, 200433, China

    Qinqin Yang, Xiao Li, Siyu Liang, Guixia Pan, Changjing Zuo & Chao Cheng

  3. Department of Military Health Statistics, Naval Medical University, Shanghai, China

    Shengyong Wu

  4. Department of Cardiology, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, 168 Changhai Road, Shanghai, 200433, China

    Xudong Xu, Xianxian Zhao & Suxuan Liu

Authors
  1. Guokun Wang
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Contributions

All authors’ material preparation and animal procedures were performed by Guokun Wang and Qinqin Yang. Data collection and analysis were performed by Shengyong Wu, Xudong Xu, Xiao Li, Siyu Liang and Guixia Pan. Changjing Zuo, Xianxian Zhao, Chao Cheng and Suxuan Liu contributed to the study conception and design. Guokun Wang, Qinqin Yang and Shengyong Wu wrote the draft of the manuscript. Chao Cheng and Suxuan Liu conceived the study and interpreted the results. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Chao Cheng or Suxuan Liu.

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Wang, G., Yang, Q., Wu, S. et al. Molecular imaging of fibroblast activity in pressure overload heart failure using [68 Ga]Ga-FAPI-04 PET/CT. Eur J Nucl Med Mol Imaging 50, 465–474 (2023). https://doi.org/10.1007/s00259-022-05984-6

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