Abstract
2906
Introduction: More diagnostic tools and further analysis of the disease are necessary to develop as the rapid spead of coronavirus disease 2019 (COVID-19). The infection of SARS-CoV-2 in human relys on the receptor-binding domain (RBD) of SARS-CoV-2 binding to human angiotensin-converting enzyme 2 (ACE2). Nanobody Nb11-59 was isolated to bind to the SARS-CoV-2-RBD to neutralize the virus with high affinity, and block the interation of ACE2 and SARS-CoV-2-RBD. Based on the non-invasive and whole body, deep tissue and high resolution/senseivite of positron emission tomography (PET) techonology, we present the evaluation of novel SRAS-Cov-2 neutralizing nanobody and detect its ability to target RBD in body.
Methods: The radiolabelling procedure of 68Ga-Nb1159 was optimized. The binding assays were completed with the SARS-CoV-2-RBD to evaluate the affinity and specificty of the 68Ga-Nb1159 probe in vitro. The biodistribution, pharmacokinetics and micro-PET imaging of the 68Ga-Nb1159 probe were researched in healthy Kunming (KM) and/or model mice treated SARS-CoV-2-RBD subcutaneously and intratracheally.
Results: The radiotracer remained high affinity to BRD (Kd = 25.53 nM), and showed reliable radio-chemical characters both in vitro and in vivo. The distribution and whole body Micro-PET of 68Ga-Nb1159 in mice exhibited rapid clearance in circulations systems, and remained robust uptakes in renal and urinary systems. 68Ga-Nb1159 could specifically visualize the distribution of SARS-CoV-2-RBD in body with the model mice treated RBD subcutaneously and intratracheally.
Conclusions: 68Ga-Nb1159 may be a promising choice for exploring the invading of SARS-CoV-2-RBD and improve understanding of the viral as a tool. Especially, this study showed a novel molecular radio agent and reliable evaluation methods aimed to SARS-CoV-2-RBD through non-invasive and visual PET technology.
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