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Visualizing dynamic changes in PD-L1 expression in non-small cell lung carcinoma with radiolabeled recombinant human PD-1

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

Abstract

Purpose

Tumor heterogeneity limits the predictive value of PD-L1 expression and influences the outcomes of the immunohistochemical assay for therapy-induced changes in PD-L1 levels. This study aimed to determine the predictive value of PD-L1 for non-small cell lung carcinoma (NSCLC), thereby developing imaging agents to non-invasively image and examine the effect of the therapeutic response to PD-L1 blockade therapy.

Methods

A cohort of 102 patients with lung cancer was analyzed, and the prognostic significance of PD-L1 expression level was investigated. Recombinant human PD-1 ECD protein (rhPD1) was expressed, purified, and labeled with 64Cu for the evaluation of PD-L1 status in tumors. Mice subcutaneously bearing PD-L1 high-expressing tumor HCC827 and PD-L1 low-expressing tumor A549 were used to determine tracer-target specificity and examine the effect of therapeutic response to PD-L1 blockade therapy.

Results

PD-L1 was proved to be a good prognosis marker for NSCLC, and its expression was correlated with the histology of NSCLC. PET imaging revealed high tumor accumulation of 64Cu-NOTA-rhPD1 in HCC827 tumors (9.0 ± 0.5%ID/g), whereas it was 3.2 ± 0.4%ID/g in A549 tumors at 3 h post-injection. The lower tumor uptake (3.1 ± 0.3%ID/g) of 64Cu-labeled denatured rhPD1 in HCC827 tumors at 3 h post-injection (p < 0.001) demonstrated the target specificity of 64Cu-NOTA-rhPD1. Furthermore, PET showed that 64Cu-NOTA-rhPD1 sensitively monitored treatment-related changes in PD-L1 expression, and seemed to be superior to [18F]FDG.

Conclusion

We identified PD-L1 as a good prognosis marker for surgically resected NSCLC and developed the PET tracer 64Cu-NOTA-rhPD1 with high target specificity for PD-L1.

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Acknowledgements

We thank the Optical Bioimaging Core Facility and the Center for Nanoscale Characterization & Devices (CNCD) of WNLO-HUST for support with data acquisition, the Analytical and Testing Center of HUST for performing spectral measurements, and the Research Core Facilities for Life Science (HUST) for using flow cytometry.

Funding

The study was in part funded by the Temares Family Fund at the Massachusetts General Hospital (AWC) and the National Natural Science Foundation of China (Grant No. 81971025; HML).

Author information

Authors and Affiliations

  1. Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, 430074, China

    Haiming Luo & Changwen Yang

  2. MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China

    Haiming Luo & Changwen Yang

  3. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Cox 308, Boston, MA, 02114, USA

    Haiming Luo & Annie W. Chan

  4. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Dong Kuang

  5. Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, Hong Kong

    Sixiang Shi

Authors
  1. Haiming Luo
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  2. Changwen Yang
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  3. Dong Kuang
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  4. Sixiang Shi
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  5. Annie W. Chan
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Contributions

LH: study design, experiments, data analysis, and manuscript writing. CA: study design. YC: data analysis. KD: clinical tissue samples. SS: help to check the manuscript. All authors reviewed and approved the final version.

Corresponding authors

Correspondence to Haiming Luo or Annie W. Chan.

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Ethics approval

The ethics committee of Tongji Medical College institutional review board at Huazhong University of Science and Technology approved the study protocol involving human tissue samples. All procedures involving animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at Massachusetts General Hospital and the Institutional Animal Care and Use Committee of Huazhong University of Science and Technology.

Competing interests

The authors declare no competing interests.

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This article is part of the Topical Collection on Preclinical Imaging

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Luo, H., Yang, C., Kuang, D. et al. Visualizing dynamic changes in PD-L1 expression in non-small cell lung carcinoma with radiolabeled recombinant human PD-1. Eur J Nucl Med Mol Imaging 49, 2735–2745 (2022). https://doi.org/10.1007/s00259-022-05680-5

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  • DOI: https://doi.org/10.1007/s00259-022-05680-5

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