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

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

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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Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Funding

This study was financially supported by the National Natural Science Foundation of China (Grant numbers 82272111, 92159303, 62027901, 82272045, 91859207, 81771873 and 82002887), the Beijing Natural Science Foundation (Grant number 7212207), the Science and Technology Innovation Team Talent Project of Hunan Province (Grant number 2021RC4056), the Natural Science Foundation of Hunan Province (Grant numbers 2023JJ30976).

Author information

Author notes

  1. Ming Zhou, Shijun Xiang, Yajie Zhao these authors contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China

    Ming Zhou, Shijun Xiang, Yajie Zhao, Yongxiang Tang, Jinhui Yang, Xiaoqin Yin & Shuo Hu

  2. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Beijing, 100190, China

    Jie Tian & Yang Du

  3. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine, Beihang University, No. 95 Zhongguancun East Road, Beijing, 100190, China

    Jie Tian

  4. National Clinical Research Center for Geriatric Disorders (Xiangya), Changsha, China

    Shuo Hu

  5. Key Laboratory of Biological Nanotechnology of National Health Commission, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, China

    Shuo Hu

  6. University of Chinese Academy of Sciences, Beijing, 100080, People’s Republic of China

    Yang Du

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  1. Ming Zhou
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Contributions

Conception, design and supervision by Yang Du, Jie Tian and Shuo Hu. Methodology was provided by Ming Zhou and Yang Du. Material preparation, data collection and analysis were performed by Shijun Xiang, Xiaoqin Yin, Jinhui Yang and Yongxiang Tang. The first draft of the manuscript was written by Yajie Zhao and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jie Tian, Shuo Hu or Yang Du.

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Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

All clinical studies were approved by the Medical Ethics Committee of Xiangya Hospital, Central South University (No. 202106115). All animal studies were performed according to the guidelines of the Animal Care Committee of Central South University (CSU-2022–0290).

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Zhou, M., Xiang, S., Zhao, Y. et al. [68Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study. Eur J Nucl Med Mol Imaging 51, 369–379 (2024). https://doi.org/10.1007/s00259-023-06447-2

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