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

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.

Noninvasive Mapping of Angiotensin Converting Enzyme-2 in Pigeons Using Micro Positron Emission Tomography

“…This observation is consistent with the results of a recent highly sensitive RNA in situ mapping study, which showed that the expression of ACE2 gradually decreased from nose to respiratory tract and was consistent with the gradient through lung epithelial culture [ 16 ]. This gradient could be clearly seen in PET images of some volunteers in other studies by our team DX600 and HZ20 showed similar Kd of 98.7 and 100.0 nm, respectively, suggesting that nucleophile 68Ga has little or no effect on the affinity of the probe [ 17 ].…”

Oncology and cardiology positron emission tomography/computed tomography faced with COVID-19: A review of available literature data

“…In a comparison of patients who had recovered from COVID-19 and volunteers, the COVID-19 recovered patients showed higher 68 Ga-HZ20 uptake in most organs. Uptake in the oropharynx, nasal mucosa, and eyes (which are exposed to virus entry) and the lungs (which are the most affected by the virus) was similar or slightly higher in recovered patients than in healthy volunteers (164). A variety of NM tracers have potential for detecting and evaluating the range of complications that can be caused by COVID-19 (165,166).…”

Current status and future perspective of radiopharmaceuticals in China

“…Some radiotracers targeting other diseases have also been developed including a purinergic receptor P2X7 antagonist [ 18 F]F-PTTP for the detection of inflammation [78], [ 99m Tc]Tc-GlcNAc-PEI (N-acetylglucosamine (GlcNAc) conjugated polyethylenimine (PEI)) specifically interacts with desmin and vimentin expressed on activated hepatic stellate cells (HSCs) for assessing liver fibrosis [79], [ 18 F] FPGal based on isotonicamide for the imaging of asialoglycoprotein receptor (ASGPR) related liver disease [80], and [ 68 Ga]Ga-HZ20 for the quantitative analysis of angiotensin Mi [48], Yu [51] Feng [49], Gao [52] Ma Xing [54] Miao [55], Huang [56] Jiang [57], Huang [58] Yang [ converting enzyme 2 (ACE2) expression in novel coronavirus sensitive organs [81].…”