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68Ga-FAPI PET visualize heart failure: from mechanism to clinic

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Heart failure (HF) is a chronic progressive clinical syndrome associated with structural and/or functional heart abnormalities. Active fibroblasts and ventricular remodelling play an essential role in HF progression. 68Ga-labelled fibroblast activation protein (FAP) inhibitor (68Ga-FAPI) binds to FAP. This study aimed to examine the feasibility of using 68Ga-FAPI positron emission tomography (PET)/computed tomography (CT) to visualize changes in cardiac fibrosis and function over time in the HF setting.

Methods

After establishing an isoproterenol (ISO)-induced HF rat model (14 consecutive days of intraperitoneal ISO injections), echocardiography and 68Ga-FAPI PET/CT were performed weekly in experimental and control groups. Rat hearts were examined weekly for biodistribution analysis; autoradiography; and haematoxylin and eosin, FAP immunofluorescence and Masson’s trichrome staining analysis. Rat blood was sampled weekly for enzyme-linked immunosorbent assay analysis of various plasma indicators. A preliminary clinical study was also performed in seven HF patients who underwent both 13N-amino (NH3) perfusion and 68Ga-FAPI cardiac PET imaging.

Results

In the animal experiments, myocardial 68Ga-FAPI uptake, expression of FAP and myocardial contractility peaked on day 7 after the initial ISO injection. Only slight fibrotic changes were observed on histopathological examination. 68Ga-FAPI uptake and ventricular wall motion decreased over time as cardiac fibrosis and degree of myocardial injury gradually increased. In the human HF patient study, 68Ga-FAPI PET imaging identified varying degrees of 68Ga-FAPI uptake in the myocardium that did not precisely match with 13N-NH3 myocardial perfusion.

Conclusion

As HF progresses, 68Ga-FAPI uptake is high in the early stages and then gradually decreases. Although preliminary, our findings suggest that 68Ga-FAPI PET can be used to demonstrate active myocardial fibrosis. Active myocardial FAP expression is followed by myocardial remodelling and fibrosis. Detection of early active FAP expression may assist treatment decision making in HF patients.

Clinical Trial Registration: NCT04982458

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Funding

This work was financially supported by the National Natural Science Foundation of China (82030052 and 81901783).

Author information

Author notes

  1. Wenyu Song, Xiao Zhang and ShuKun He contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Wenyu Song, Xiao Zhang, Yongkang Gai, Chunxia Qin, Fan Hu & Xiaoli Lan

  2. Hubei Key Laboratory of Molecular Imaging, Wuhan, China

    Wenyu Song, Xiao Zhang, ShuKun He, Yongkang Gai, Chunxia Qin, Fan Hu, Jing Wang & Xiaoli Lan

  3. Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, Hubei Province, China

    ShuKun He & Jing Wang

  4. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Yan Wang & Zhaohui Wang

  5. Department of Cardiac Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Peng Bai

Authors
  1. Wenyu Song
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Contributions

X. L. conceived and designed the study devised and supervised the project. X. Z. and W. S. finished the animal experiments and wrote the manuscript. J. W. and S. H. performed routine transthoracic echocardiography. Y. G. synthesized the probe. C. Q. and F. H. analysed the image data. Y. W., Z. W. and P. B. contributed to patient clinical data analysis.

Corresponding authors

Correspondence to Xiao Zhang, Jing Wang or Xiaoli Lan.

Ethics declarations

Ethics approval

This study was approved by the Clinical Research Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (no. 20210617-01), and registered at the Clinical Trail (NCT04982458).

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All subjects gave written informed consent.

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The authors declare no competing interests.

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This article is part of the Topical Collection on Cardiology

Supplementary Information

ESM 1

Table of radioactivity accumulation and H/M values in heart section (PDF) (DOCX 22.8 kb)

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Song, W., Zhang, X., He, S. et al. 68Ga-FAPI PET visualize heart failure: from mechanism to clinic. Eur J Nucl Med Mol Imaging 50, 475–485 (2023). https://doi.org/10.1007/s00259-022-05994-4

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