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Early detection of anthracycline-induced cardiotoxicity using [68 Ga]Ga-FAPI-04 imaging

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Abstract

Purpose

Anthracycline-induced cardiotoxicity (AIC), whose major manifestation is diffuse myocardial fibrosis, is an important clinical problem in cancer therapy. Therefore, early identification and treatment are clinically important. This study aims to explore the feasibility of using 68 Ga-labelled fibroblast activation protein (FAP) inhibitor ([68 Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) for the early identification of the fibrotic process and guidance of antifibrosis therapy in AIC.

Methods

An AIC rat model was induced by the intravascular administration of doxorubicin (DOX) once per week for 1, 2, 3 and 6 weeks (2.5 mg/kg/injection, groups 1–4), whereas intravascular saline was administered to control rats. Experimental and control groups (n = 4) underwent [68 Ga]Ga-FAPI PET/CT following disease induction. Groups 5 and 6 received DOX injections for 3 and 6 weeks, treated with angiotensin-converting enzyme (ACE) inhibitor starting at 3 weeks, treated with enalapril (20 mg/kg, gastric gavage) daily and underwent echocardiography and [68 Ga]Ga-FAPI PET/CT at 3 weeks after treatment. Rat hearts were subjected to haematoxylin and eosin staining, FAP immunohistochemistry, Sirius red staining and Masson’s trichrome staining to investigate the pathological changes and deposition of collagen fibres. Rat blood was sampled weekly for the enzyme-linked immunosorbent assay of various markers of myocardial injury, such as plasma cardiac troponin I, B-type natriuretic peptide and angiotensin II.

Results

[68 Ga]Ga-FAPI-04 uptake by the heart was significantly higher in the cardiotoxicity group than in the control group at weeks 3 (SUVmax: 1.21 ± 0.23 vs 0.67 ± 0.01, P < 0.05) and 6 (SUVmax: 1.48 ± 0.28 vs 0.67 ± 0.08, P < 0.001), whereas left ventricle ejection fraction (LVEF) did not significantly differ between normal and AIC rats at week 3. FAP+ expression began to increase starting at week 3, before irreversible fibrotic changes were detected, until week 6. After 3 weeks of enalapril treatment, [68 Ga]Ga-FAPI-04 accumulation decreased in groups 5 and 6 (SUVmax decreased from 1.21 ± 0.23 to 0.77 ± 0.08 and 1.48 ± 0.28 to 1.09 ± 1.06, P < 0.05). Cardiac function was preserved (LVEF was 75.7% ± 7.38% in group 3 vs 74.5% ± 2.45% in group 5, P > 0.05) and improved (LVEF increased from 51.6% ± 9.03% in group 4 to 65.2% ± 4.27% in group 6, P < 0.05), and myocardial fibrosis attenuated (from 6.5% ± 1.2% in group 4 to 4.31% ± 0.37% in group 6, P < 0.01).

Conclusion

[68 Ga]Ga-FAPI PET/CT can be used for the early detection of active myocardial fibrosis in AIC and the evaluation of the efficacy of therapeutic interventions. Early treatment guided by [68 Ga]Ga-FAPI PET/CT may reduce anthracycline-induced myocardial injury and improve heart function.

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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 research was supported by the National Key Research and Development Program of China (No. 2021YFF0501400 and 2021YFF0501404) and National Natural Science Foundation of China (No. 22277002 and 92059101).

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Author notes

  1. Zhuxin Wei and Hongchuang Xu contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of MRI, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Rd 167, Xicheng District, Beijing, 100037, China

    Zhuxin Wei, Jiaxin Wang & Shihua Zhao

  2. Department of Nuclear Medicine, Peking University First Hospital, Xishiku Rd 8, Xicheng District, Beijing, 100034, China

    Hongchuang Xu & Xing Yang

  3. Department of Nuclear Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8Th Gongtinanlu Rd, Chaoyang District, Beijing, 100020, China

    Bixi Chen & Min-Fu Yang

  4. Department of Central Laboratory, Peking University First Hospital, Beijing, 100034, China

    Xing Yang

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Contributions

All authors’ material preparation and animal procedures were performed by Zhuxin Wei and Hongchuang Xu. Data collection and analysis were performed by Zhuxin Wei and Hongchuang Xu. Hongchuang Xu, Zhuxin Wei, Bixi Chen, Jiaxin Wang, Min-Fu Yang, Xing Yang and Shihua Zhao contributed to the study conception and design. Zhuxin Wei wrote the draft of the manuscript. Min-Fu Yang, Xing Yang and Shihua Zhao conceived the study and interpreted the results. All authors read and approved the final manuscript.

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Correspondence to Xing Yang, Min-Fu Yang or Shihua Zhao.

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Wei, Z., Xu, H., Chen, B. et al. Early detection of anthracycline-induced cardiotoxicity using [68 Ga]Ga-FAPI-04 imaging. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06673-2

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