18 F-CC-Omi-X PET in Characterizing Lipid Metabolism via ACE2 Mapping

Dysregulated lipid metabolism, as seen in obesity, is closely linked to altered angiotensin-converting enzyme 2 (ACE2) expression in adipose tissue. However, real-time noninvasive monitoring of ACE2 dynamics in vivo remains a significant challenge. Therefore, we developed 18F-CC-Omi-X (Omi-X: HQPYRVVVLSFELLH), an ACE2-targeted PET tracer specifically designed for mapping ACE2 in lipid metabolic contexts. l-Propargylglycine (l-Pra) was modified to the C-terminus of Omi-X to suit 18F-labeling via the click-chemistry protocol, which minimized steric hindrance and preserved superior binding specificity compared to conventional N-terminus modification, as evidenced by a favorable IC50 (421 nM) in competitive binding assays. In diet-induced obese humanized ACE2 (hACE2) mice, 18F-CC-Omi-X PET showed high and specific uptake in adipose depots, with SUVmax strongly correlating with ex vivo ACE2 levels (r = 0.961, P < 0.05). Crucially, intervention with the ACE2 modulator ursodeoxycholic acid (UDCA) led to a significant decrease in tracer uptake in both subcutaneous and mesenteric fat, thereby enabling visualization of pharmacologically induced ACE2 downregulation in vivo. This work established 18F-CC-Omi-X as a vital molecular imaging tracer, enabling the noninvasive quantification of ACE2 dynamics directly within key lipid metabolic tissues, which is essential for elucidating its role in metabolic diseases and evaluating targeted therapies.