Development of novel peptide-based radiotracers for detecting PD-L1 expression and guiding cancer immunotherapy

Zhu, Shiyu; Liang, Beibei; Zhou, Yuxuan; Chen, Yinfei; Fu, Jiayu; Qiu, Ling; Lin, Jianguo

doi:10.1007/s00259-023-06480-1

Eur J Nucl Med Mol Imaging

2023

DOI: 10.1007/s00259-023-06480-1

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Development of novel peptide-based radiotracers for detecting PD-L1 expression and guiding cancer immunotherapy

Shiyu Zhu,

Beibei Liang,

Yuxuan Zhou

et al.

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2024

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Cited by 3 publications

References 40 publications

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Challenges coexist with opportunities: development of a macrocyclic peptide PET radioligand for PD-L1

Huang,

Son,

et al. 2024

Eur J Nucl Med Mol Imaging

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Challenges coexist with opportunities: development of a macrocyclic peptide PET radioligand for PD-L1

Huang,

Son,

et al. 2024

Eur J Nucl Med Mol Imaging

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Comparative study of [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p as novel PD-L1 targeting PET probes for tumor imaging

Bai,

Sun,

Huang

et al. 2024

Bioorganic Chemistry

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A PD-L1-Targeted Probe Cy5.5-A11 for In Vivo Imaging of Multiple Tumors

Cao,

Mao,

et al. 2024

ACS Omega

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PD-L1 is an immune checkpoint molecule mediating cancer immune escape, and its expression level in the tumor has been used as a biomarker to predict response to immune checkpoint inhibitor (ICI) therapy. Our previous study reveals that an 11 amino acid-long ANXA1-derived peptide (named A11) binds and degrades the PD-L1 protein in multiple cancers and is a potential peptide for cancer diagnosis and treatment. Near-infrared fluorescence (NIF) optical imaging of tumors offers a noninvasive method for detecting cancer and monitoring therapeutic responses. In this study, an NIF dye Cy5.5 was conjugated with A11 peptide to develop a novel PD-L1-targeted probe for molecular imaging of tumors and monitor the dynamic changes in PD-L1 expression in tumors. In vitro imaging studies showed that intense fluorescence was observed in triplenegative breast cancer MDA-MB-231, nonsmall cell lung cancer H460, and melanoma A375 cells incubated with Cy5.5-A11, and the cellular uptake of Cy5.5-A11 was efficiently inhibited by coincubation with unlabeled A11 or knockdown of cellular PD-L1 by shRNA. In vivo imaging studies showed accumulation of Cy5.5-A11 in the MDA-MB-231, H460, and A375 xenografts with good contrast from 0.5 to 24 h after intravenous injection, indicating that Cy5.5-A11 possesses the strong ability for in vivo tumor imaging. Moreover, the fluorescent signal of A11-Cy5.5 in the xenografts was successfully blocked by coinjection of unlabeled A11 peptide or knockdown of cellular PD-L1 by shRNA, indicating the specificity of Cy5.5-A11 targeting PD-L1 in tumor imaging. Our data demonstrate that Cy5.5-A11 is a novel tool for tumor imaging of PD-L1, which has the potential for detecting cancer and predicting ICI therapeutic responses.

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Development of novel peptide-based radiotracers for detecting PD-L1 expression and guiding cancer immunotherapy

Cited by 3 publications

References 40 publications

Challenges coexist with opportunities: development of a macrocyclic peptide PET radioligand for PD-L1

Challenges coexist with opportunities: development of a macrocyclic peptide PET radioligand for PD-L1

Comparative study of [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p as novel PD-L1 targeting PET probes for tumor imaging

A PD-L1-Targeted Probe Cy5.5-A11 for In Vivo Imaging of Multiple Tumors

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