Rou Li, Aijing Xu, Chao Cheng, Jian Chen, Mingxin Wang, Xiu Luo, Siyu Liang, Wenli Hou, Bin Cui, Yu Feng, Changjing Zuo, Xiao Li

ACE2 PET in healthy and diseased conditions

  • Biomedical Engineering
  • Biomaterials

AbstractAngiotensin converting enzyme 2 (ACE2) played a critical role in regulating renin‐angiotensin‐aldosterone system (RAAS). In this research, 68Ga‐cyc‐DX600 was synthesized as PET tracer of ACE2 imaging. ACE2 positron emission tomography/magnetic resonance (PET/MR) was preliminary administered on twelve healthy volunteers, and the images were normalized and registered to establish the standard model of ACE2 PET. In diseased conditions, 68Ga‐cyc‐DX600 PET and 18F‐FDG PET were compared for COVID‐19 (one in acute phase and three in post‐COVID), anemia (n = 1) and malignancies (n = 2) to evaluate the diagnostic efficiency. 68Ga‐cyc‐DX600 PET was of a definite ACE2 dependence. For the tracer uptake of ACE2 PET/MR of female and male, differences existed in salivary glands, upper respiratory tract and kidneys, meanwhile, age, and body mass index (BMI) were also the confounding factors. RAAS‐related tissue and organs were of the relatively higher tracer uptake, such as SUVmean of cardiac chamber (3.786 ± 1.495), liver (5.342 ± 2.267), spleen (4.465 ± 2.508), and kidney (4.906 ± 1.619 for female and 8.431 ± 5.179 for male). For COVID‐19, ACE2 PET revealed ACE2 fluctuations, particularly in the susceptible organs, including liver, spleen and testis. In the case of anemia, the activated local RAS in the bone marrow was of diffuse high tracer uptake. ACE2 PET of malignancies added supplementary information to FDG PET. 68Ga‐cyc‐DX600‐based ACE2 PET models were established for visually monitoring of whole‐body ACE2 expression. The feasibility of ACE2 PET in supervising disease was primarily proved in COVID‐19, anemia and malignancies as providing a comprehensive view on the disease process and functional recovery.

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