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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 8/2022

02-02-2022 | Radiotherapy | Original Article

Galectin expression detected by 68Ga-galectracer PET as a predictive biomarker of radiotherapy resistance

Authors: Dehua Lu, Haoyi Zhou, Nan Li, Yanpu Wang, Ting Zhang, Fei Wang, Ning Liu, Hua Zhu, Jinming Zhang, Zhi Yang, Zhaofei Liu

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2022

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Abstract

Purpose

Hypoxia is a hallmark of solid tumors that is related to radiotherapy resistance. As galectin members, such as galectin-1 and galectin-3, are associated with tumor hypoxia, herein we aimed to investigate whether positron emission tomography (PET) imaging of galectin expression can be employed to effectively pinpoint tumor hypoxia, and to predict radiotherapy resistance.

Methods

We synthesized a galectin-targeting radiotracer, designated 68Ga-galectracer, by radiolabeling a thiodigalactoside derivative. The properties of 68Ga-galectracer for PET imaging of tumor hypoxia were characterized in three tumor hypoxia mouse models. Additionally, preliminary PET/CT was performed in two patients with lung cancer to investigate the potential application of 68Ga-galectracer for clinical imaging.

Results

High-contrast imaging was achieved in the murine acute hypoxia tumor model, A549 natural hypoxia model, and sorafenib treatment-induced hypoxic 4T1 tumor model by PET using 68Ga-galectracer. In fact, 68Ga-galectracer exhibited superior hypoxia detection to that of 18F-misonidazole in the 4T1 tumors. Moreover, tumors with high galectin expression levels, as detected by 68Ga-galectracer PET, exhibited significantly lower responses to subsequent radiotherapy compared to those with low galectin expression levels. In patients with lung cancer, PET imaging using 68Ga-galectracer provided data that were complementary to that of the glucose metabolic PET radiotracer 18F-fluorodeoxyglucose.

Conclusion

68Ga-galectracer is a promising radiotracer for PET-based imaging of tumor hypoxia in vivo. Thus, hypoxia PET with 68Ga-galectracer could provide a noninvasive approach to proactively predict radiotherapy efficacy.

Trial registration

Chictr.org.cn (ChiCTR2000029522). Registered 03 February 2020.
Appendix
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Metadata
Title
Galectin expression detected by 68Ga-galectracer PET as a predictive biomarker of radiotherapy resistance
Authors
Dehua Lu
Haoyi Zhou
Nan Li
Yanpu Wang
Ting Zhang
Fei Wang
Ning Liu
Hua Zhu
Jinming Zhang
Zhi Yang
Zhaofei Liu
Publication date
02-02-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05711-1

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