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
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Cerenkov 发光成像是评估体内结直肠癌 PD-L1 水平的有效临床前工具
DOI：
10.1186/s13550-020-00654-w
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发表时间：
2020
期刊：
影响因子：
3.2
通讯作者：
Hongbo Hu
中科院分区：
文献类型：
--
作者：
Sheng Zhao;Wenbin Pan;Huijie Jiang;Rongjun Zhang;Hao Jiang;Zonghui Liang;Hongbo Hu
背景临床前和临床研究表明，免疫治疗能有效延缓肿瘤进展，抗PD-1/PD-L1治疗的临床疗效与肿瘤中PD-L1的表达水平有关。为了研究131 I标记的抗PD-L1单克隆抗体（131 I-PD-L1-Mab）在结直肠癌移植瘤小鼠体内的无创性Cerenkov发光显像靶向能力，研制了131 I-PD-L1-Mab示踪剂（131I-PD-L1-Mab），体外结合实验评价131 I-PD-L1-Mab与PD-L1的亲和力及与不同大肠癌细胞的结合水平，并与流式细胞术、免疫印迹分析和免疫荧光染色进行比较。结果131 I-PD-L1-Mab对PD-L1具有较高的亲和力，平衡解离常数为1.069 × 10- 9 M。竞争抑制实验进一步证实了131 I-PD-L1-Mab的特异性结合能力。在具有不同PD-L1表达的四种不同荷瘤模型中，生物分布和Cerenkov发光成像显示，RKO肿瘤对示踪剂131 I-PD-L1-Mab的吸收最高，结论131 I-PD-L1-Mab Cerenkov无创性显像在评价肿瘤PD-L1状态方面具有很大的潜力。L1表达和选择患者进行抗PD-L1靶向治疗。
BackgroundPreclinical 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. A131I-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.MethodAnti-PD-L1 monoclonal antibody labeled with131I (131I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of131I-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 of131I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.Results131I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069 × 10-9M. The competitive inhibition assay further confirmed the specific binding ability of131I-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 tracer131I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% IA/g at 48 h.ConclusionsThere is a great potential for131I-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.