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Granzyme B PET imaging inflammation and remodeling in myocardial infarction

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

Abstract

Purpose

This study aimed to evaluate whether granzyme B (GzmB)-targeted positron emission tomography (PET) imaging agent (68 Ga-grazytracer) can characterize cardiac inflammation and remodeling in myocardial infarction (MI).

Methods

Rats with MI were subjected to GzmB-targeted PET/CT on post-operative days 1, 3, 6, 14, and 28. Autoradiography, Masson staining, immunohistochemistry, and ELISA were performed to verify the inflammatory response and remodeling after MI in vitro. Rats were treated with GzmB inhibitor Z-IETD-FMK to improve cardiac remodeling. Cardiac function tests were performed by echocardiography at 6 weeks after MI.

Results

The highest uptake of 68 Ga-grazytracer was observed on day 3 after MI compared with the values obtained on the other days (0.294 ± 0.03% ID/g at 3 days vs. 0.122 ± 0.01% ID/g in the sham group, P < 0.001). Immunohistochemistry showed significantly high expression of GzmB and CD8, in line with the PET/CT imaging results. Autoradiography revealed 68 Ga-grazytracer accumulation in the infarcted myocardium. The 68 Ga-grazytracer uptake of treated rats was significantly reduced compared with that in the MI groups (0.184 ± 0.03%ID/g vs. 0.286 ± 0.03%ID/g; P < 0.001). Echocardiography showed that the left ventricular ejection fraction was lower in the MI groups than in the ischemia reperfusion group. GzmB inhibitor treatment was shown to be effective in improving cardiac function without significantly shortening infarct size.

Conclusions

This study demonstrated the potential of 68 Ga-grazytracer imaging to delineate adverse inflammatory responses and pathological cardiac remodeling, which can help predict heart function. PET/CT imaging-guided therapy may reduce myocardial injury and improve heart function in MI.

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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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Acknowledgements

We thank Yi Tian and Tiantian Mou (Department of Nuclear Medicine, Beijing Anzhen Hospital) for their help in PET/CT imaging and MI models establishment.

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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Authors and Affiliations

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

    Hongchuang Xu & Xing Yang

  2. 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

  3. Department of Nuclear Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China

    Bixi Chen

  4. Department of Cardiology, Peking University First Hospital, Xishiku Rd 8, Xicheng District, Beijing, 100034, China

    Haoyu Weng & Jianping Li

  5. 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 Hongchuang Xu and Zhuxin Wei. Data collection and analysis were performed by Hongchuang Xu and Zhuxin Wei. Hongchuang Xu, Zhuxin Wei, Bixi Chen, Jiaxin Wang, Haoyu Weng and Jianping Li contributed to the study conception and design. Zhuxin Wei wrote the draft of the manuscript. Jianping Li, 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 Jianping Li, Xing Yang or Shihua Zhao.

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

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Xu, H., Wei, Z., Chen, B. et al. Granzyme B PET imaging inflammation and remodeling in myocardial infarction. Eur J Nucl Med Mol Imaging 51, 991–1001 (2024). https://doi.org/10.1007/s00259-023-06521-9

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