Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan, China.
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China.
J Med Virol. 2023 Nov;95(11):e29221. doi: 10.1002/jmv.29221.
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, poses a significant threat to public health. Angiotensin-converting enzyme 2 (ACE2) is a key receptor for SARS-CoV-2 infection. Recombinant human ACE2 (RhACE2), as a soluble supplement for human ACE2, can competitively block SARS-CoV-2 infection. In this study, a mouse organ in situ rhACE2 high aggregation model was constructed for the first time, and in vivo real-time positron emission tomography (PET) imaging of rhACE2 in the mouse model was performed using an ACE2-specific agent Ga-HZ20. This radiotracer exhibits reliable radiochemical properties in vitro and maintains a high affinity for rhACE2 in vivo. In terms of probe uptake, Ga-HZ20 showed a good target-to-nontarget ratio and was rapidly cleared from the circulatory system and excreted by the kidneys and urinary system. PET imaging with this radiotracer can noninvasively and accurately monitor the content and distribution of rhACE2 in the body, which clarifies that rhACE2 can aggregate in multiple organs, suggesting the preventive and therapeutic potential of rhACE2 for SARS-CoV-2 and COVID-19.
新型冠状病毒病（COVID-19）由严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）感染引起，对公共卫生构成重大威胁。血管紧张素转换酶 2（ACE2）是 SARS-CoV-2 感染的关键受体。重组人 ACE2（RhACE2）作为人 ACE2 的可溶性补充剂，可以竞争性地阻断 SARS-CoV-2 感染。本研究首次构建了小鼠原位 rhACE2 高聚集模型，并使用 ACE2 特异性示踪剂 Ga-HZ20 对小鼠模型中的 rhACE2 进行了体内实时正电子发射断层扫描（PET）成像。该放射性示踪剂在体外具有可靠的放射化学性质，并在体内保持对 rhACE2 的高亲和力。在探针摄取方面，Ga-HZ20 显示出良好的靶标与非靶标比，并能迅速从循环系统中清除，通过肾脏和泌尿系统排泄。使用该放射性示踪剂进行 PET 成像可以非侵入性且准确地监测体内 rhACE2 的含量和分布，这表明 rhACE2 可以在多个器官中聚集，提示 rhACE2 对 SARS-CoV-2 和 COVID-19 具有预防和治疗潜力。
