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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

08-12-2023 | Radioimmunotherapy | Original Article

[¹⁷⁷Lu]Lu-labeled anti-claudin-18.2 antibody demonstrated radioimmunotherapy potential in gastric cancer mouse xenograft models

Authors: Ziqing Zeng, Liqiang Li, Jinping Tao, Jiayue Liu, Hongjun Li, Xueming Qian, Zhi Yang, Hua Zhu

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2024

Abstract

Purpose

Gastric cancer (GC), one of the most prevalent and deadliest tumors worldwide, is often diagnosed at an advanced stage with limited treatment options and poor prognosis. The development of a CLDN18.2-targeted radioimmunotherapy probe is a potential treatment option for GC.

Methods

The CLDN18.2 antibody TST001 (provided by Transcenta) was conjugated with DOTA and radiolabeled with the radioactive nuclide ¹⁷⁷Lu. The specificity and targeting ability were evaluated by cell uptake, imaging and biodistribution experiments. In BGC823^CLDN18.2/AGS^CLDN18.2 mouse models, the efficacy of [¹⁷⁷Lu]Lu-TST001 against CLDN18.2-expressing tumors was demonstrated, and toxicity was evaluated by H&E staining and blood sample testing.

Results

[¹⁷⁷Lu]Lu-TST001 was labeled with an 99.17%±0.32 radiochemical purity, an 18.50 ± 1.27 MBq/nmol specific activity and a stability of ≥ 94% after 7 days. It exhibited specific and high tumor uptake in CLDN18.2-positive xenografts of GC mouse models. Survival studies in BGC823^CLDN18.2 and AGS^CLDN18.2 tumor-bearing mouse models indicated that a low dose of 5.55 MBq and a high dose of 11.10 MBq [¹⁷⁷Lu]Lu-TST001 significantly inhibited tumor growth compared to the saline control group, with the 11.1 MBq group showing better therapeutic efficacy. Histological staining with hematoxylin and eosin (H&E) and Ki67 immunohistochemistry of residual tissues confirmed tumor tissue destruction and reduced tumor cell proliferation following treatment. H&E showed that there was no significant short-term toxicity observed in the heart, spleen, stomach or other important organs when treated with a high dose of [¹⁷⁷Lu]Lu-TST001, and no apparent hematotoxicity or liver toxicity was observed.

Conclusion

In preclinical studies, [¹⁷⁷Lu]Lu-TST001 demonstrated significant antitumor efficacy with acceptable toxicity. It exhibits strong potential for clinical translation, providing a new promising treatment option for CLDN18.2-overexpressing tumors, including GC.

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Title: [177Lu]Lu-labeled anti-claudin-18.2 antibody demonstrated radioimmunotherapy potential in gastric cancer mouse xenograft models
Authors: Ziqing Zeng
Liqiang Li
Jinping Tao
Jiayue Liu
Hongjun Li
Xueming Qian
Zhi Yang
Hua Zhu
Publication date: 08-12-2023
Publisher: Springer Berlin Heidelberg
Keywords: Radioimmunotherapy
Gastric Cancer
Gastric Cancer
Radionuclide Therapy
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2024
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06561-1

At a glance: The STEP trials

Springer Medicine

[¹⁷⁷Lu]Lu-labeled anti-claudin-18.2 antibody demonstrated radioimmunotherapy potential in gastric cancer mouse xenograft models

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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