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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

28.09.2023 | Original Article

[⁶⁸Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study

verfasst von: Ming Zhou, Shijun Xiang, Yajie Zhao, Yongxiang Tang, Jinhui Yang, Xiaoqin Yin, Jie Tian, Shuo Hu, Yang Du

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2024

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Abstract

Purpose

PD-L1 PET imaging, as a non-invasive procedure, can perform a real-time, dynamic and quantitative analysis of PD-L1 expression at tumor sites. In this study, we developed a novel peptide-based PET tracer, [⁶⁸ Ga]Ga-AUNP-12, for preclinical and first-of-its-kind imaging of PD-L1 expression in patients.

Methods

Radiosynthesis of [⁶⁸ Ga]Ga-AUNP-12 was conducted. Assays for cellular uptake and binding were conducted on the PANC02, CT26, and B16F10 cell lines. Preclinical models were used to investigate its biodistribution, imaging capacity, and pharmacokinetics. Furthermore, interferon-γ (IFN-γ) was used for development of an animal model with high PD-L1 expression for targeted PET imaging and efficacy evaluation of PD-L1 blocking therapy. In healthy volunteers and cancer patients, the PD-L1 imaging, radiation dosimetry, safety, and biodistribution were further evaluated.

Results

In vitro and in vivo animal studies showed that [⁶⁸ Ga]Ga-AUNP-12 PET imaging displayed a high specificity in evaluating PD-L1 expression. The radiochemical yield of [⁶⁸ Ga]Ga-AUNP-12 was 71.7 ± 8.2%. Additionally, its molar activity and radiochemical purity were satisfactory. The B16F10 tumor was visualized with the tumor uptake of 6.86 ± 0.71% ID/g and tumor-to-muscle ratio of 6.83 ± 0.36 at 60 min after [⁶⁸ Ga]Ga-AUNP-12 injection. Furthermore, [⁶⁸ Ga]Ga-AUNP-12 PET imaging could sensitively detect the PD-L1 dynamic changes in CT26 tumor xenograft models regulated by IFN-γ treatment, and correspondingly can effectively guide immunotherapy. Regarding radiation dosimetry, [⁶⁸ Ga]Ga-AUNP-12 is safe for human use. The first human study found that [⁶⁸ Ga]Ga-AUNP-12 can be rapidly cleared from blood and other nonspecific organs through the kidney excretion, leading to form a clear imaging contrast in the clinical framework. The specificity of [⁶⁸ Ga]Ga-AUNP-12 was validated and tumor uptake strongly correlated with the high PD-L1 expression in patients with lung adenocarcinoma and oesophageal squamous cell carcinoma (OSCC).

Conclusion

[⁶⁸ Ga]Ga-AUNP-12 was successfully developed as a PD-L1-specific PET imaging tracer in preclinical and first-in-human studies.

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Titel: [68Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study
verfasst von: Ming Zhou
Shijun Xiang
Yajie Zhao
Yongxiang Tang
Jinhui Yang
Xiaoqin Yin
Jie Tian
Shuo Hu
Yang Du
Publikationsdatum: 28.09.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2024
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06447-2

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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