Evaluation of SARS-CoV-2-Neutralizing Nanobody Using Virus Receptor Binding Domain-Administered Model Mice
Song Liu,
Guanghui Li,
Lei Ding,
Jin Ding,
Qian Zhang,
Dan Li,
Xingguo Hou,
Xiangxing Kong,
Jing Zou,
Shiming Zhang,
Hongbin Han,
Yakun Wan,
Zhi Yang,
Hua Zhu
Affiliations
Song Liu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China; Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China
Guanghui Li
Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai, China
Lei Ding
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Jin Ding
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
Qian Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
Dan Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
Xingguo Hou
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
Xiangxing Kong
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
Jing Zou
Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology, Peking University Third Hospital, Beijing 100191, China
Shiming Zhang
Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology, Peking University Third Hospital, Beijing 100191, China
Hongbin Han
Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology, Peking University Third Hospital, Beijing 100191, China; Department of Radiology, Peking University Third Hospital, Peking University, Beijing 100191, China
Yakun Wan
Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai, China
Zhi Yang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China; Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China; Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China
Hua Zhu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China; Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China; Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China
Due to the rapid spread of coronavirus disease 2019 (COVID-19), there is an urgent requirement for the development of additional diagnostic tools for further analysis of the disease. The isolated nanobody Nb11-59 binds to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) with high affinity to neutralize the virus and block the angiotensin-converting enzyme 2- (ACE2-) RBD interaction. Here, we introduce a novel nanobody-based radiotracer named 68Ga-Nb1159. The radiotracer retained high affinity for the RBD and showed reliable radiochemical characteristics both in vitro and in vivo. Preclinical positron emission tomography (PET) studies of 68Ga-Nb1159 in mice revealed its rapid clearance from circulation and robust uptake into the renal and urinary systems. Fortunately, 68Ga-Nb1159 could specifically reveal the distribution of the RBD in mice. This study also helped to evaluate the pharmacodynamic effects of the neutralizing nanobody. Moreover, 68Ga-Nb1159 may be a promising tool to explore the distribution of the RBD and improve the understanding of the virus. In particular, this study identified a novel molecular radioagent and established a reliable evaluation method for specifically investigating the RBD through noninvasive and visual PET technology.
