Objectives The aim of this study was to assess the potential of noninvasive and repeated monitoring of rhACE2 distribution and content in organs using the ACE2-specific nuclide probe ⁶⁸Ga-HZ20. Methods We optimized the labeling conditions of the probe and evaluated its safety. A mouse organ in situ rhACE2 high-aggregation model was constructed for the first time, and in vivo real-time PET imaging of rhACE2 was performed using the ACE2-specific PET agent ⁶⁸Ga-HZ20. The distribution and uptake of the probe were analyzed, and the model was validated. Results This radiotracer exhibited reliable radiochemical properties in vitro and maintained a high affinity for rhACE2 in vivo. In terms of probe uptake, ⁶⁸Ga-HZ20 showed a good target-to-nontarget ratio, and the correlation between the uptake value of the probe and the dose of rhACE2 was >90% in both models; the probe was rapidly cleared from the circulatory system and excreted by the kidneys and urinary system. No organs were damaged after the injection of high doses of probe. Conclusions This technology for noninvasively and repeatedly monitoring the content and distribution of rhACE2 in vivo aids in clarifying the resident capacity of rhACE2 in organs and in analyzing the preventive effect of rhACE2 against SARS-CoV-2 and the effectiveness of therapies for COVID-19.