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

Zhu, Hua; Zhang, Hanwen; Zhou, Nina; Ding, Jin; Jiang, Jinquan; Liu, Teli; Liu, Ziyu; Wang, Feng; Zhang, Qian; Zhang, Zhuochen; Yan, Shi; Li, Lei; Benabdallah, Nadia; Jin, Hongjun; Liu, Zhaofei; Cai, Lisheng; Thorek, Daniel L. J.; Yang, Xing; Yang, Zhi

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.