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Adv Sci (Weinh) ; 8(16): e2100965, 2021 08.
Article in English | MEDLINE | ID: covidwho-1281195

ABSTRACT

Rapid progress has been made to identify and study the causative agent leading to coronavirus disease 2019 (COVID-19) but many questions including who is most susceptible and what determines severity remain unanswered. Angiotensin-converting enzyme 2 (ACE2) is a key factor in the infection process of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this study, molecularly specific positron emission tomography imaging agents for targeting ACE2 are first developed, and these novel agents are evaluated in vitro, in preclinical model systems, and in a first-in-human translational ACE2 imaging of healthy volunteers and a SARS-CoV-2 recovered patient (NCT04422457). ACE2 expression levels in different organs in live subjects are quantitatively delineated and observable differences are measured in the patient recovered from COVID-19. Surprising sites of uptake in the breast, reproductive system and very low uptake in pulmonary tissues are reported. This novel method can add a unique tool to facilitate SARS-CoV-2 related research and improve understanding of this enigmatic disease. Molecular imaging provides quantitative annotation of ACE2, the SARS-CoV-2 entry receptor, to noninvasively monitor organs impacted by the COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/virology , Peptides/pharmacokinetics , SARS-CoV-2/metabolism , Animals , COVID-19/pathology , Cells, Cultured , Female , Gallium Radioisotopes/pharmacokinetics , Humans , Male , Mice , Positron Emission Tomography Computed Tomography , Protein Binding , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Tissue Distribution , Xenograft Model Antitumor Assays
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