核素标记的PD-1抗体用于肿瘤成像
  • 制备(89)Zr-Df-纳武单抗示踪剂,采用人源化肺癌小鼠模型,体内示踪表达PD-1肿瘤浸润性T细胞的生物分布;
  • 体内外表达PD-1的活化T细胞与示踪剂的结合增加,通过靶向肿瘤和人源化A549荷瘤小鼠腮腺内局部活化T细胞表达PD-1,(89)Zr-Df-纳武单抗的PET成像可清晰描绘皮下肿瘤;
  • T细胞在腮腺和泪腺的浸润清晰,并通过组织学确认;
  • PD-1靶向药可体内成像肿瘤,有助于新的免疫治疗的设计和研发、疾病诊断、监测和患者分层。
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!

(89)Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer

(89)Zr标记的纳武单抗在人源化小鼠肺癌模型中成像T细胞浸润

10.1007/s00259-017-3803-4

2017-08-19, Article

Abstract & Authors:展开

Abstract:收起
PURPOSE: Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes.
METHODS: (89)Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung cancer. The tracer was developed by radiolabeling the antibody with the positron emitter zirconium-89 ((89)Zr). Imaging results were validated by ex vivo biodistribution studies, and PD-1 expression was validated by immunohistochemistry. Data obtained from PET imaging were used to determine human dosimetry estimations.
RESULTS: The tracer showed elevated binding to stimulated PD-1 expressing T-cells in vitro and in vivo. PET imaging of (89)Zr-Df-nivolumab allowed for clear delineation of subcutaneous tumors through targeting of localized activated T-cells expressing PD-1 in the tumors and salivary glands of humanized A549 tumor-bearing mice. In addition to tumor uptake, salivary and lacrimal gland infiltration of T-cells was noticeably visible and confirmed via histological analysis.
CONCLUSIONS: These data support our claim that PD-1-targeted agents allow for tumor imaging in vivo, which may assist in the design and development of new immunotherapies. In the future, noninvasive imaging of immunotherapy biomarkers may assist in disease diagnostics, disease monitoring, and patient stratification.

First Authors:
Christopher G England

Correspondence Authors:
Peng Huang,Weibo Cai

All Authors:
Christopher G England,Dawei Jiang,Emily B Ehlerding,Brian T Rekoske,Paul A Ellison,Reinier Hernandez,Todd E Barnhart,Douglas G McNeel,Peng Huang,Weibo Cai

评论