Molecular PET/CT Profiling of ACE2 Expression In Vivo: Implications for Infection and Outcome from SARS-CoV-2

Adv Sci (Weinh). 2021 Aug;8(16):e2100965. doi: 10.1002/advs.202100965. Epub 2021 Jun 26.

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.

Keywords: angiotensin-converting enzyme 2; human; positron emission tomography imaging; severe acute respiratory syndrome coronavirus-2; translational research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • DX600 peptide
  • Gallium Radioisotopes
  • Peptides
  • Angiotensin-Converting Enzyme 2