Research Paper Volume 13, Issue 9 pp 13006—13022
A preclinical study: correlation between PD-L1 PET imaging and the prediction of therapy efficacy of MC38 tumor with 68Ga-labeled PD-L1 targeted nanobody
- 1 Tianjin Medical University, Tianjin 300070, P.R. China
- 2 Department of Radiation Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China
- 3 School of Graduate Studies, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 271099, P.R. China
- 4 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250017, P.R. China
- 5 Department of Radiation Oncology, The Fourth People’s Hospital of Jinan, Jinan 250031, P.R. China
- 6 School of Pharmacy, Yantai University, Yantai 264003, P.R. China
- 7 Smart Nuclide Biotech, Suzhou 215123, P.R. China
- 8 School of Clinical Medicine, Weifang Medical University, Weifang 261053, P.R. China
- 9 Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250017, P.R. China
Received: May 28, 2020 Accepted: February 16, 2021 Published: April 27, 2021https://doi.org/10.18632/aging.202981
How to Cite
Copyright: © 2021 Qin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Although immunotherapy has achieved great clinical success in clinical outcomes, especially the anti-PD-1 or anti-PD-L1 antibodies, not all patients respond to anti-PD-1 immunotherapy. It is urgently required for a clinical diagnosis to develop non-invasive imaging meditated strategy for assessing the expression level of PD-L1 in tumors. In this work, a 68Ga-labeled single-domain antibody tracer, 68Ga-NOTA-Nb109, was designed for specific and noninvasive imaging of PD-L1 expression in an MC38 tumor-bearing mouse model. Comprehensive studies including Positron Emission Tomography (PET), biodistribution, blocking studies, immunohistochemistry, and immunotherapy, have been performed in differences PD-L1 expression tumor-bearing models. These results revealed that 68Ga-NOTA-Nb109 specifically accumulated in the MC38-hPD-L1 tumor. The content of this nanobody in MC38 hPD-L1 tumor and MC38 Mixed tumor was 8.2 ± 1.3, 7.3 ± 1.2, 3.7 ± 1.5, 2.3 ± 1.2%ID/g and 7.5 ± 1.4, 3.6 ± 1.7, 1.7 ± 0.6, 1.2 ± 0.5%ID/g at 0.5, 1, 1.5, 2 hours post-injection, respectively. 68Ga-NOTA-Nb109 has the potential to further noninvasive PET imaging and therapy effectiveness assessments based on the PD-L1 status in tumors. To explore the possible synergistic effects of immunotherapy combined with chemotherapy, MC38 xenografts with different sensitivity to PD-L1 blockade were established. In addition, we found that PD-1 blockade also had efficacy on the PD-L1 knockout tumors. RT-PCR and immunofluorescence analysis were used to detect the expression of PD-L1. It was observed that both mouse and human PD-L1 expressed among three types of MC38 tumors. These results suggest that PD-L1 on tumor cells affect the efficacy, but it on host myeloid cells might be essential for checkpoint blockade. Moreover, anti–PD-1 treatment activates tumor-reactive CD103+ CD39+ CD8+T cells (TILs) in tumor microenvironment.
PD-1: programmed cell death protein-1; PD-L1: programmed death protein ligand 1; TILs: tumor infiltrating immune cells; PET: positron emission tomography; IHC: immune- histochemistry; HuMAb: human immunoglobulin monoclonal antibody; IF: immunofluorescence; HPLC: High-Performance Liquid Chromatography; SEC: size-exclusion chromatogram; RTV: relative tumor volume; hPD-L1: human PD-L1; KO: knock out.