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European Journal of Nuclear Medicine and Molecular Imaging

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22-11-2023 | Myocardial Infarction | Original Article

Granzyme B PET imaging inflammation and remodeling in myocardial infarction

Authors: Hongchuang Xu, Zhuxin Wei, Bixi Chen, Jiaxin Wang, Haoyu Weng, Jianping Li, Xing Yang, Shihua Zhao

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2024

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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Title: Granzyme B PET imaging inflammation and remodeling in myocardial infarction
Authors: Hongchuang Xu
Zhuxin Wei
Bixi Chen
Jiaxin Wang
Haoyu Weng
Jianping Li
Xing Yang
Shihua Zhao
Publication date: 22-11-2023
Publisher: Springer Berlin Heidelberg
Keywords: Myocardial Infarction
Positron Emission Tomography
Computed Tomography
Computed Tomography
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2024
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06521-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Granzyme B PET imaging inflammation and remodeling in myocardial infarction

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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