1. Academic Validation
  2. Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

  • EJNMMI Res. 2020 Jun 15;10(1):64. doi: 10.1186/s13550-020-00654-w.
Sheng Zhao 1 Wenbin Pan 1 Huijie Jiang 2 Rongjun Zhang 3 Hao Jiang 1 Zonghui Liang 4 Hongbo Hu 1
Affiliations

Affiliations

  • 1 Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 2 Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. jianghuijie@hrbmu.edu.cn.
  • 3 Jiangsu Institute of Nuclear Medicine, Wuxi, China. zhangrongjun@jsinm.org.
  • 4 Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China. liangzhjhj@163.com.
Abstract

Background: Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131I-labeled anti-PD-L1 monoclonal antibody tracer, 131I-PD-L1-Mab, was developed to study the target ability of noninvasive Cerenkov luminescence imaging in colorectal Cancer xenograft mice.

Method: Anti-PD-L1 monoclonal antibody labeled with 131I (131I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131I-PD-L1-Mab to PD-L1 and their binding level to different colorectal Cancer cells, and compared with flow cytometry, Western blot analysis, and immunofluorescence staining. The clinical application value of 131I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.

Results: 131I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069 × 10-9 M. The competitive inhibition assay further confirmed the specific binding ability of 131I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% IA/g at 48 h.

Conclusions: There is a great potential for 131I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.

Keywords

Cerenkov luminescence imaging; Colorectal cancer; Immunotherapy; Preclinical tool; Programmed death ligand-1.

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