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Sensitive and quantitative in vivo analysis of PD-L1 using magnetic particle imaging and imaging-guided immunotherapy

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

An Editorial to this article was published on 21 March 2023

Abstract

Purpose

The programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) expression correlate with the immunotherapeutic response rate. The sensitive and non-invasive imaging of immune checkpoint biomarkers is favorable for the accurate detection and characterization, image-guided immunotherapy in cancer precision medicine. Magnetic particle imaging (MPI), as a novel and emerging imaging modality, possesses the advantages of high sensitivity, no image depth limitation, positive contrast, and absence of radiation. Hence, in this study, we performed the pioneer investigation of monitoring PD-L1 expression using MPI and the MPI-guided immunotherapy.

Methods

We developed anti-PD-L1 antibody (aPDL1)-conjugated magnetic fluorescent hybrid nanoparticles (MFNPs-aPDL1) and utilized MPI in combination with fluorescence imaging (FMI) to dynamically monitor and quantify PD-L1 expression in various tumors with different PD-L1 expression levels. The ex vivo real-time polymerase chain reaction (qPCR), western blotting, and immunofluorescence staining analysis were further performed to validate the in vivo imaging observation. Moreover, the MPI was further performed for the guidance of immunotherapy.

Results

Our data showed that PD-L1 expression can be specifically and sensitively monitored and quantified using MPI and FMI imaging methods, which were validated by ex vivo qPCR and western blotting analysis. In addition, MPI-guided PD-L1 immunotherapy can enhance the effectiveness of cancer immunotherapy.

Conclusion

To our best knowledge, this is the pioneer study to utilize MPI in combination with a newly developed MFNPs-aPDL1 imaging probe to dynamically visualize and quantify PD-L1 expression in tumor microenvironment. This imaging strategy may facilitate the clinical optimization of immunotherapy management.

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Data availability

All data relevant to the study are included in the article or uploaded as supplemental information.

Abbreviations

PD-1:

Programmed cell death protein-1

PD-L1:

Programmed cell death ligand-1

MPI:

Magnetic particle imaging

FMI:

Fluorescence molecular imaging

aPDL1:

Anti-PD-L1 antibody

MFNP:

Magnetic fluorescent nanoparticle

PET:

Positron emission tomography

NIR:

Near-infrared

qPCR:

Real-time polymerase chain reaction

TEM:

Transmission electron microscopy

ROI:

Region of interest

ALT:

Alanine transaminase

AST:

Aspartate transaminase

ALP:

Alkaline phosphatase

TBR:

Tumor-to-background ratio

IFN-γ:

Interferon-γ

EPR:

Enhanced permeability and retention

FOV:

Field of view

PBS:

Phosphate-buffered saline

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Acknowledgements

The authors would like to acknowledge the instrumental and technical support of multi-modal biomedical imaging experimental platform, Institute of Automation, Chinese Academy of Sciences.

Funding

This work was funded by National Natural Science Foundation of China under Grant Nos 62027901, 82272111, 92159303, 81871514, 81227901, 81470083, and 81527805; Beijing Natural Science Foundation under Grant No. 7212207; the National Key Research and Development Program of China under Grant No. 2017YFA0700401; and Shenzhen Science and Technology Program (JCYJ20210324140205013).

Author information

Author notes

  1. Zhengyao Peng, Chang Lu, and Guangyuan Shi contributed equally to this work.

Authors and Affiliations

  1. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China

    Zhengyao Peng, Guangyuan Shi, Lin Yin, Jie Tian & Yang Du

  2. University of Chinese Academy of Sciences, Beijing, 100080, China

    Zhengyao Peng, Lin Yin & Yang Du

  3. State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Shenzhen Research Institution of Hunan University, Hunan University, Changsha, 410082, China

    Chang Lu & Guosheng Song

  4. University of Science and Technology of China, Hefei, 230026, China

    Guangyuan Shi

  5. Department of Ultrasound, Peking University Third Hospital, Beijing, 100191, China

    Xiaolong Liang

  6. Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Medicine, Beihang University, Beijing, 100191, China

    Jie Tian

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  1. Zhengyao Peng
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Contributions

The concept and study design were conceived by Yang Du, Jie Tian, and Guosheng Song. Zhengyao Peng, Chang Lu, Guangyuan Shi, and Lin Yin performed the study and data analysis. Yang Du, Zhengyao Peng, and Chang Lu prepared the manuscript. Jie Tian and Guosheng Song edited the manuscript.

Corresponding authors

Correspondence to Guosheng Song, Jie Tian or Yang Du.

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Ethics approval

Four- to five-week-old male BALB/c mice and nude mice were got from the Vital River Laboratory Animal Technology Corporation (Beijing, China). All animal handling procedures were strictly based on the guidelines of the Institutional Animal Care and Use Committee (Permit No: IA21-2203–24) at the Institute of Automation, Chinese Academy of Sciences.

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All the co-authors approved the manuscript and agreed with submission to your esteemed journal.

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Peng, Z., Lu, C., Shi, G. et al. Sensitive and quantitative in vivo analysis of PD-L1 using magnetic particle imaging and imaging-guided immunotherapy. Eur J Nucl Med Mol Imaging 50, 1291–1305 (2023). https://doi.org/10.1007/s00259-022-06083-2

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