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Early detection of radiation-induced myocardial damage by [18F]AlF-NOTA-FAPI-04 PET/CT imaging

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

Abstract

Purpose

Retrospective analysis revealed increased [18F]AlF-NOTA-FAPI-04 uptake in the myocardium of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). This study investigated and verified the feasibility of [18F]AlF-NOTA-FAPI-04 PET/CT for detecting radiation-induced myocardial damage (RIMD).

Methods

Myocardial FAPI uptake was analyzed before and during radiotherapy in thirteen ESCC patients treated with CCRT. In the animal study, a single dose of 50 Gy was delivered to the cardiac apex of Wistar rats (24 rats, including 16 RIMD model rats and 8 control model rats). RIMD model rats were scanned with [18F]AlF-NOTA-FAPI-04 PET/CT weekly for 12 weeks, and left ventricular ejection fraction (LVEF) was measured by magnetic resonance imaging. Dynamic, blocking, and [18F]FDG PET/CT studies (4 rats/group) were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted.

Results

Increased FAPI uptake in the myocardium was found after CCRT (1.53 ± 0.53 vs 1.88 ± 0.70, P = 0.015). In RIMD rats, significantly increased FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure and peaked in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardium than in the remote myocardium, as identified by decreased [18F]FDG uptake and confirmed by autoradiography, hematoxylin–eosin, Masson’s trichrome, and immunohistochemical staining. The LVEF remained unchanged at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week.

Conclusion

Through clinical phenomena and animal experimental studies, this study indicated that [18F]AlF-NOTA-FAPI-04 PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF, indicating the clinical potential of [18F]AlF-NOTA-FAPI-04 as a PET/CT tracer for early monitoring of RIMD.

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Availability of data and material

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

All software applications or custom code are available in the public repository.

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Funding

Jinming Yu has received grants from the Academic Promotion Program of Shandong First Medical University (2019ZL002); the Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences (2019RU071); the National Natural Science Foundation of China (81627901, 81972863, and 82030082); and the Natural Science Foundation of Shandong (ZR201911040452). Yuchun Wei has received grants from the Natural Science Foundation of Shandong Province (ZR2021QH008).

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Authors and Affiliations

  1. Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China

    Yuchun Wei, Xueting Qin, Yuanyuan Tao & Jinming Yu

  2. Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Yuhong Sun

  3. Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Junyan Liu

  4. Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China

    Gongsen Zhang, Shengnan Xu, Shijie Wang, Jinli Pei & Jinming Yu

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  1. Yuchun Wei
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Contributions

Jinming Yu and Jinli Pei conceived of the study and participated in its design. Yuchun Wei participated in the experiments and drafted the manuscript. Xueting Qin and Yuanyuan Tao are responsible for collecting PET/CT images. Gongsen Zhang carried out the nuclear medicine. Yuhong Sun and Junyan Liu carried out the pathology. Shengnan Xu conducted the statistical analysis. Shijie Wang prepared the [18F]AlF-NOTA-FAPI-04 and [18F]FDG. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jinli Pei or Jinming Yu.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the local ethics committee of Shandong Cancer Hospital and Institute, and the patients gave written, informed consent before the study.

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All authors of the current manuscript meet the specified criteria for authorship and agreed to publish this manuscript.

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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

Supplementary Table 1

(DOCX 17 kb)

Supplementary Fig. 1

Dose distributions in the transverse, sagittal, and coronal sections and dose–volume histogram (DVH). (PDF 113 kb)

Supplementary Fig. 2

(A) Long-axis and short-axis of a RIMD rat heart. (B) Short-axis end-systolic and end-diastolic time frames from a cine of the control and RIMD rat (3rd week after radiation) using IG-FLASH scans. (C) Short-axis end-systolic and end-diastolic time frames from a cine of the control and RIMD rat (8th week after radiation) using IG-FLASH scans. (PDF 118 kb)

Supplementary Fig. 3

Change in rat weight throughout the study. (PNG 22 kb)

High resolution image (TIF 93 kb)

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Wei, Y., Sun, Y., Liu, J. et al. Early detection of radiation-induced myocardial damage by [18F]AlF-NOTA-FAPI-04 PET/CT imaging. Eur J Nucl Med Mol Imaging 50, 453–464 (2023). https://doi.org/10.1007/s00259-022-05962-y

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