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

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

doi:10.1016/j.jpha.2022.09.001

Cited by 17 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, replacement of DOTA with other chelators has the potential to reduce the liver accumulation. Furthermore, suitable models showed overexpression of PD-L1 should be used to evaluate the promising radiotracers …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Linear Peptide-Based PET Tracers for Imaging PD-L1 in Tumors

Zhang

Jiang

et al. 2023

Mol. Pharmaceutics

View full text Add to dashboard Cite

Programmed cell death receptor 1 (PD-1) and its ligand PD-L1 are particularly interesting immune checkpoint proteins for human cancer treatment. Positron emission tomography (PET) imaging allows for the dynamic monitoring of PD-L1 status during tumor progression, thus informing patients’ response index. Herein, we report the synthesis of two linear peptide-based radiotracers, [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202, and validate their utility for PD-L1 visualization in preclinical models. The precursor peptide HKP2201 was derived from a linear peptide ligand, CLP002, which was previously identified by phage display and showed nanomolar affinity toward PD-L1. Appropriate modification of CLP002 via PEGylation and DOTA conjugation yielded HKP2201. The dimerization of HKP2201 generated HKP2202. The 64Cu and 68Ga radiolabeling of both precursors was studied and optimized. PD-L1 expression in mouse melanoma cell line B16F10, mouse colon cancer cell line MC38, and their allografts were assayed by immunofluorescence and immunohistochemistry staining. Cellular uptake and binding assays were conducted in both cell lines. PET imaging and ex vivo biodistribution studies were employed in tumor mouse models bearing B16F10 and MC38 allografts. [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202 were obtained with satisfactory radiocharacteristics. They all showed lower liver accumulation compared to [64Cu]/[68Ga]WL12. B16F10 and MC38 cells and their tumor allografts sections were verified to express PD-L1. These tracers demonstrated a concentration-dependent cell affinity and a comparable half-maximal effect concentration (EC50) with radiolabeled WL12. Competitive binding and blocking studies demonstrated the specific target of these tracers to PD-L1. PET imaging and ex vivo biodistribution studies revealed notable tumor uptake in tumor-bearing mice and rapid clearance from blood and major organs. Importantly, [64Cu]/[68Ga]HKP2202 showed higher tumor uptake compared to [64Cu]/[68Ga]HKP2201. Of note, [64Cu] labeled tracers showed longer retention in tumors than [68Ga] labeled traces, indicating advantages in the long-term tracking of PD-L1 dynamics. In comparison, [68Ga]HKP2201 and [68Ga]HKP2202 showed lower liver accumulation, enabling its great potential in the fast detection of both primary and metastatic tumors, including hepatic carcinoma. [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202 are promising PET tracers for visualizing PD-L1 status. Notably, their combination would cooperate in rapid diagnosis and subsequent treatment guidance. Future assessment of the radiotracers in patients is needed to fully evaluate their clinical value.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Furthermore, suitable models showed overexpression of PD-L1 should be used to evaluate the promising radiotracers. 37…”

Section: ■ Discussionmentioning

confidence: 99%

Linear Peptide-Based PET Tracers for Imaging PD-L1 in Tumors

Zhang

Jiang

et al. 2023

Mol. Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Similar experimental results were also reported in the literature. 18,40 In the future, other chemotherapy drugs with stronger targeting specificity and fewer side effects instead of CDDP will be selected to reduce the high signal in the background of tumor-bearing mice. As a whole, these results indicated that chemotherapy could induce the upregulation of PD-L1 and the dynamic changes of PD-L1 expression could be detected sensitively and specifically by [ 68 Ga]Ga-NOTA-Cy5-R1 through PET/NIRF imaging.…”

Section: Discussionmentioning

confidence: 99%

“…The fluorescence imaging and PET imaging were carried out when the tumor volume reached about 200–300 mm 3 . For PD-L1 induction models, NCI-H1299 tumor was selected and the treatment was described in our previous protocol. , All experiments involving animals were conducted according to the Animal Care and Ethics Committee of Jiangsu Institute of Nuclear Medicine (JSINM-2021-129 and JSINM-2022-042).…”

Section: Methodsmentioning

confidence: 99%

Multifunctional Probe Based on “Chemical Antibody–Aptamer” for Noninvasive Detection of PD-L1 Expression in Cancer

Kong,

Liu,

Chen

et al. 2023

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

“…Notably, their results showed that 68 Ga-NODA-CDV-Nb109 PET imaging could sensitively monitor the upregulation of PD-L1 expression induced by chemotherapeutic agents (Doxorubicin), which facilitated timely interventional therapy. It is important to consider that Doxorubicin treatment may induce systemic toxicity, so it is expected that a less toxic therapy for non-target tissues will be selected in the future to further evaluate whether 68 Ga-NODA-CDV-Nb109 is suitable for the dynamic monitoring of changes in PD-L1 expression levels in cancer [135].…”

Section: Single-domain Antibodiesmentioning

confidence: 99%

Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy

Zhang¹,

Wu²,

Zhao³

et al. 2023

J. Cancer

View full text Add to dashboard Cite

Programmed death-1 is a protein found on the surface of immune cells that can interact with its ligand, programmed death-ligand 1 (PD-L1), which is expressed on the plasma membrane, the surface of secreted cellular exosomes, in cell nuclei, or as a circulating soluble protein. This interaction can lead to immune escape in cancer patients. In clinical settings, PD-L1 plays an important role in tumor disease diagnosis, determining therapeutic effectiveness, and predicting patient prognosis. PD-L1 inhibitors are also essential components of tumor immunotherapy. Thus, the detection of PD-L1 levels is crucial, especially in the era of precision cancer therapy. In recent years, innovations have been made in traditional immunoassay methods and the development of new immunoassays for PD-L1 detection. This review aims to summarize recent research progress in tumor PD-L1 detection technology and highlight the clinical applications of PD-L1.

show abstract

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

Cited by 17 publications

References 42 publications

Linear Peptide-Based PET Tracers for Imaging PD-L1 in Tumors

Linear Peptide-Based PET Tracers for Imaging PD-L1 in Tumors

Multifunctional Probe Based on “Chemical Antibody–Aptamer” for Noninvasive Detection of PD-L1 Expression in Cancer

Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy

Contact Info

Product

Resources

About