1. Academic Validation
  2. Radioimmunotherapy study of 131I-labeled Atezolizumab in preclinical models of colorectal cancer

Radioimmunotherapy study of 131I-labeled Atezolizumab in preclinical models of colorectal cancer

  • EJNMMI Res. 2022 Oct 28;12(1):70. doi: 10.1186/s13550-022-00939-2.
Linhan Zhang 1 2 Sheng Zhao 2 Huijie Jiang 3 Rongjun Zhang 4 Mingyu Zhang 5 Wenbin Pan 2 Zhongqi Sun 2 Dandan Wang 2 Jinping Li 2
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 2 Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 3 Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. [email protected].
  • 4 Jiangsu Institute of Nuclear Medicine, Wuxi, China. [email protected].
  • 5 Department of Nuclear Medicine, Beijing Friendship Hospital, Affiliated to Capital Medical University, Beijing, China. [email protected].
Abstract

Background: Programmed cell death 1 ligand 1(PD-L1) is overexpressed in many tumors. The radionuclide-labeled anti-PD-L1 monoclonal antibody can be used for imaging and therapy of PD-L1 overexpressing Cancer. Here, we described 131I-labeled Atezolizumab (131I-Atezolizumab, targeting PD-L1) as a therapeutic agent for colorectal Cancer with PD-L1 overexpression.

Methods: 131I-Atezolizumab was prepared by the Iodogen method. The expression levels of PD-L1 in different human colorectal cells were determined by flow cytometry, western blot and cell binding assay. The immunoreactivity of 131I-Atezolizumab to PD-L1 high-expressing cells was determined by immunoreactive fraction. The killing abilities of different concentrations of 131I-Atezolizumab on cells with high and low expression of PD-L1 were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Cerenkov luminescence imaging (CLI) and radioimmunotherapy (RIT) of 131I-Atezolizumab were performed on two human colorectal Cancer models. The distribution and tumor targeting of 131I-Atezolizumab were evaluated by imaging. Tumor volume and survival time were used as indicators to evaluate the anti-tumor effect of 131I-Atezolizumab.

Results: The expression level of PD-L1 in vitro determined by the cell binding assay was related to the data of flow cytometry and western blot. 131I-Atezolizumab can specifically bind to PD-L1 high-expressing cells in vitro to reflect the expression level of PD-L1. Immunoreactive fraction of PD-L1 high-expressing RKO cells with 131I-Atezolizumab was 52.2%. The killing ability of 131I-Atezolizumab on PD-L1 high-expressing cells was higher than that of low-expressing cells. CLI proved that the specific uptake level of tumors depends on the expression level of PD-L1. Effect of 131I-Atezolizumab RIT showed an activity-dependent tumor suppressor effect on RKO tumor-bearing mice with high PD-L1 expression. 131I-Atezolizumab (37 MBq) can improve the median survival time of mice (34 days), compared to untreated mice (27 days) (P = 0.027). Although a single activity(37 MBq) of 131I-Atezolizumab also inhibited the tumors of HCT8 tumor-bearing mice with low PD-L1 expression (P < 0.05), it could not prolong the survival of mice(P = 0.29).

Conclusion: 131I-Atezolizumab can be used as a CLI agent for screening PD-L1 expression levels. It may be used as a radioimmunotherapy drug target for PD- L1 overexpressing tumors.

Keywords

Cerenkov luminescence imaging; Colorectal cancer; Molecular imaging; Programmed cell death 1 ligand 1; Radioimmunotherapy.

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