Liu Song, Li Guanghui, Ding Lei, Ding Jin, Zhang Qian, Li Dan, Hou Xingguo, Kong Xiangxing, Zou Jing, Zhang Shiming, Han Hongbin, Wan Yakun, Yang Zhi, Zhu Hua
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.
Research (Wash D C). 2022 Jul 22;2022:9864089. doi: 10.34133/2022/9864089. eCollection 2022.
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 Ga-Nb1159. The radiotracer retained high affinity for the RBD and showed reliable radiochemical characteristics both and . Preclinical positron emission tomography (PET) studies of Ga-Nb1159 in mice revealed its rapid clearance from circulation and robust uptake into the renal and urinary systems. Fortunately, Ga-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, Ga-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.
由于2019冠状病毒病（COVID-19）的迅速传播，迫切需要开发更多诊断工具以对该疾病进行进一步分析。分离出的纳米抗体Nb11-59以高亲和力结合严重急性呼吸综合征冠状病毒2（SARS-CoV-2）受体结合域（RBD），以中和病毒并阻断血管紧张素转换酶2（ACE2）-RBD相互作用。在此，我们介绍一种名为Ga-Nb1159的新型基于纳米抗体的放射性示踪剂。该放射性示踪剂对RBD保持高亲和力，并且在[具体条件1]和[具体条件2]下均显示出可靠的放射化学特性。Ga-Nb1159在小鼠中的临床前正电子发射断层扫描（PET）研究显示其从循环中快速清除，并在肾脏和泌尿系统中大量摄取。幸运的是，Ga-Nb1159能够特异性地揭示小鼠体内RBD的分布。这项研究还有助于评估中和纳米抗体的药效学作用。此外，Ga-Nb1159可能是探索RBD分布并增进对该病毒理解的一种有前景的工具。特别是，本研究鉴定出一种新型分子放射性药物，并建立了一种可靠的评估方法，通过非侵入性和可视化PET技术特异性研究RBD。
