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Evaluation of a novel monoclonal antibody mAb109 by immuno-PET/fluorescent imaging for noninvasive lung adenocarcinoma diagnosis

Authors: Hua Zhu1,2, Te-li Liu1, Chang-hao Liu2, Jing Wang2, Hong Zhang3, Bin Dong3, Jing Shen3, Chuan-ke Zhao4, Zhen-fu Li3, Zhen Cheng2, Zhi Yang1
1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
2 Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, Stanford, CA CA94305, USA
3 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, China
4 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Correspondence to: Zhen Cheng: zcheng@stanford.edu, Zhi Yang: pekyz@163.com,
DOI: 10.1038/s41401-019-0294-9
Received: 17 March 2019
Accepted: 17 July 2019
Advance online: 18 September 2019

Abstract

Monoclonal antibodies are believed to be magic bullets and hold great potential for lots of biological process. About 100 μg of mAb109 was expressed in 5 × 106 cells after 10 days’ immunization. 64Cu-NOTA-mAb109 was synthesized with the specific activity of 0.74 MBq/μg and high in vitro stability. The binding affinity of 64Cu-NOTA-mAb109 in A549 cells was determined to be 29.64 nM. 64Cu-NOTA-mAb109 displayed prominent tumor accumulation from 2 h to 60 h p.i. (9.34 ± 0.67 %ID/g). NIRF imaging of Cy5.5-mAb109 showed high accumulation till 9 days p.i., while tumors nearly can not be observed in negative groups, which was confirmed by autoradiography. Immunohistological study confirmed that mAb109 had strong and specific capacity to bind lung adenocarcinoma (concentration to 58 nM). Our study demonstrated mAb109 was a new platform for the development of novel agent for lung adenocarcinoma noninvasive imaging. The resulted 64Cu-NOTA-mAb109/Cy5.5-mAb109 show favorable imaging properties/specificity for A549 tumor and high sensitivity to human lung adenocarcinoma tissues.
Keywords: human lung adenocarcinoma; 64Cu-NOTA-mAb109; antibody production; positron-emission tomography (PET) imaging; NIRF imaging

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