Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer

Yinfei Chen; Shiyu Zhu; Jiayu Fu; Jianguo Lin; Yan Sun; Gaochao Lv; Minhao Xie; Tao Xu; Ling Qiu

doi:10.1016/j.jpha.2022.09.001

Volume 12 Issue 6

Dec. 2022

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Yinfei Chen, Shiyu Zhu, Jiayu Fu, Jianguo Lin, Yan Sun, Gaochao Lv, Minhao Xie, Tao Xu, Ling Qiu. Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer[J]. Journal of Pharmaceutical Analysis, 2022, 12(6): 869-878. doi: 10.1016/j.jpha.2022.09.001

Citation:

Yinfei Chen, Shiyu Zhu, Jiayu Fu, Jianguo Lin, Yan Sun, Gaochao Lv, Minhao Xie, Tao Xu, Ling Qiu. Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer[J]. Journal of Pharmaceutical Analysis, 2022, 12(6): 869-878. doi: 10.1016/j.jpha.2022.09.001

Citation:

Yinfei Chen, Shiyu Zhu, Jiayu Fu, Jianguo Lin, Yan Sun, Gaochao Lv, Minhao Xie, Tao Xu, Ling Qiu. Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer[J]. Journal of Pharmaceutical Analysis, 2022, 12(6): 869-878. doi: 10.1016/j.jpha.2022.09.001

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Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer

doi: 10.1016/j.jpha.2022.09.001

Yinfei Chen^a,b,
Shiyu Zhu^a,b,
Jiayu Fu^a,b,
Jianguo Lin^a,b,
Yan Sun^c,
Gaochao Lv^a,b,
Minhao Xie^a,b,
Tao Xu^{c
,
,},
Ling Qiu^{a,b
,
,}

a. NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China;
b. Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China;
c. Smart Nuclide Biopharma Co., Ltd., Suzhou, Jiangsu, 215123, China

Funds:

The authors acknowledge the financial support from the National Natural Science Foundation of China (Grant No.: 22076069), the Natural Science Foundation of Jiangsu Province (Grant No.: BK20201135), the Major Scientific Research Project of Jiangsu Commission of Health (Grant No.: ZDA2020007), and the Science Technology and Development Project of Wuxi (Grant No.: Y20212013).

Received Date: Apr. 10, 2022
Accepted Date: Sep. 13, 2022
Rev Recd Date: Sep. 06, 2022
Publish Date: Dec. 26, 2022

Abstract

Abstract

Despite advances in immunotherapy for the treatment of cancers, not all patients can benefit from programmed cell death ligand 1 (PD-L1) immune checkpoint blockade therapy. Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level; hence, accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects. Therefore, based on the high affinity antibody Nb109, a new site-specifically radiolabeled tracer, ⁶⁸Ga-NODA-cysteine, aspartic acid, and valine (CDV)-Nb109, was designed and synthesized to accurately monitor PD-L1 expression. The tracer ⁶⁸Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95% and radiochemical purity of 97%. It showed high affinity for PD-L1 with a dissociation constant of 12.34 ± 1.65 nM. Both the cell uptake assay and positron emission tomography (PET) imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells. Meanwhile, dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression, allowing timely interventional immunotherapy. In conclusion, this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
- Single-domain antibody,
- Site-specific labeling,
- Immuno-PET imaging,
- PD-L1

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References(43)

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