Radioimmunoimaging and targeting treatment in an immunocompetent murine model of triple‐negative breast cancer using radiolabeled anti–programmed death‐ligand 1 monoclonal antibody

Abstract

The overall aim of this study was to evaluate whether iodine-131 radiolabeled monoclonal antibody (mAb) targeting programmed death-ligand 1 (PD-L1) can be used for imaging of PD-L1 expression noninvasively in vivo and playing synergistic effect combined with immunotherapy. Anti-PD-L1 mAb was radiolabeled with iodine-131 ( I-PD-L1 mAb) and was characterized in vitro. Biodistribution and imaging in vivo were performed periodically. Therapy study was conducted in triple-negative breast cancer-bearing BALB/c mice. As results, the labeling efficiencies of I-PD-L1 mAb reached 80% ± 3%, with radiochemical purity of 97% ± 1%. I-PD-L1 mAb preserved the capacity to bind living PD-L1-expressing cells specifically in vitro. Tumor radioactivity uptake of I-PD-L1 mAb was significantly higher than that of control groups. The xenografts were clearly imaged from 48 to 72 hours noninvasively after injection of I-PD-L1 mAb, while the xenografts were not imaged in control groups. Tumor growth was significantly inhibited, and median survival time was remarkably prolonged in combination therapy group compared with control groups. It was concluded that I-PD-L1 mAb can be a potential theranostic candidate for visualizing of PD-L1 expression noninvasively and performing synergistic therapy in carcinomas.

Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

“…A 89 Zr-labeled mAb against mouse PD-L1 was used to show increased tracer uptake in a syngeneic head and neck tumor model after fractionated radiotherapy (Kikuchi et al 2017). Other research teams have also successfully employed mAbs for imaging of PD-L1 using different radionuclides, including 89 Zr, 111 In, 64 Cu and 131 I (Hettich et al 2016;Chatterjee et al 2016;Josefsson et al 2016;Nedrow et al 2017aNedrow et al , 2017bLesniak et al 2016;Li et al 2018;Moroz et al 2018;Truillet et al 2018;Pang et al 2018).…”

Role of medical imaging for immune checkpoint blockade therapy: From response assessment to prognosis prediction

“…Preclinical studies showed that immuno‐PET monitoring of CD8+ T cells could serve as a predictive and prognostic biomarker for immune checkpoint therapy . Currently, effective efforts are underway to define PD‐L1 or PD‐1 expression using noninvasive molecular probes, of which a large number of studies focused on the feasibility of antibody‐based tracers in immunotherapy …”

“…With regard to SPECT/CT‐based molecular imaging, several studies showed the capacity of 111 In labeled anti‐PD‐L1 antibodies for imaging PD‐L1 expression in triple‐negative breast cancer (TNBC) and NSCLC . Furthermore, Pang et al demonstrated that 131 I‐PD‐L1 monoclonal antibody (mAb) could be a potential tool for noninvasively visualizing PD‐L1 expression in primary tumors and metastases . More recently, Bensch et al conducted a first‐in‐human study to assess the potential of 89 Zr‐atezolizumab in predicting the treatment response to PD‐L1 blockade in 22 patients across three tumors types (bladder cancer, NSCLC, and TNBC) .…”

“…71,72 Currently, effective efforts are underway to define PD-L1 or PD-1 expression using noninvasive molecular probes, of which a large number of studies focused on the feasibility of antibody-based tracers in immunotherapy. [73][74][75][76][77][78][79][80][81][82] For PET/CT-based molecular imaging, 64 Cu and 89 Zr are the most common radionuclides used in immuno-oncology. HTXM-MST 64 Cu-, 89 Zr-labeled antibodies 74,77,79 PD-L1 expression -HTXM-MST 89 Zr-, 64 Cu-labeled antibodies 81,82 PD-1 expression -HTXM-MST 89 Zr-labeled antibody 83 TR; PFS, OS…”

“…73,75,76 Furthermore, Pang et al demonstrated that 131 I-PD-L1 monoclonal antibody (mAb) could be a potential tool for noninvasively visualizing PD-L1 expression in primary tumors and metastases. 78 More recently, Bensch et al conducted a first-inhuman study to assess the potential of 89 Zr-atezolizumab in predicting the treatment response to PD-L1 blockade in 22 patients across three tumors types (bladder cancer, NSCLC, and TNBC). 83 They firstly imaged PD-L1 status across inflammatory tissues and normal lymphoid tissues in human patients and found that the uptake of tracers before treatment seemed to be a robust biomarker to predict clinical responses and prognosis of patients.…”