biostudies-literatureWang JSwiss National Science FoundationPSI - Paul Scherrer Institute9-21https://www.ebi.ac.uk/biostudies/studies/S-EPMC11599313biostudies-literatureUnknown52(1)<h4>Purpose</h4>The angiotensin converting enzyme 2 (ACE2) plays a regulatory role in the cardiovascular system and serves SARS-CoV-2 as an entry receptor. The aim of this study was to synthesize and evaluate radiofluorinated derivatives of the ACE2 inhibitor MLN-4760. [¹⁸F]F-MLN-4760 and [¹⁸F]F-Aza-MLN-4760 were demonstrated to be suitable for non-invasive imaging of ACE2, potentially enabling a better understanding of its expression dynamics.<h4>Methods</h4>Computational molecular modeling, based on the structures of human ACE2 (hACE2) and mouse ACE2 (mACE2), revealed that the ACE2-binding modes of F-MLN-4760 and F-Aza-MLN-4760 were similar to that of MLN-4760. Co-crystallization of the hACE2/F-MLN-4760 protein complex was performed for confirmation. Displacement exEuropean journal of nuclear medicine and molecular imagingDevelopment of radiofluorinated MLN-4760 derivatives for PET imaging of the SARS-CoV-2 entry receptor ACE2.PMC11599313188978190414310030210456Mu LSchibli RVaccarin CTanriver MDeupi XHe YBenoit RMuller CBeyer DBode JWWang JfalseDevelopment of radiofluorinated MLN-4760 derivatives for PET imaging of the SARS-CoV-2 entry receptor ACE2.<h4>Purpose</h4>The angiotensin converting enzyme 2 (ACE2) plays a regulatory role in the cardiovascular system and serves SARS-CoV-2 as an entry receptor. The aim of this study was to synthesize and evaluate radiofluorinated derivatives of the ACE2 inhibitor MLN-4760. [¹⁸F]F-MLN-4760 and [¹⁸F]F-Aza-MLN-4760 were demonstrated to be suitable for non-invasive imaging of ACE2, potentially enabling a better understanding of its expression dynamics.<h4>Methods</h4>Computational molecular modeling, based on the structures of human ACE2 (hACE2) and mouse ACE2 (mACE2), revealed that the ACE2-binding modes of F-MLN-4760 and F-Aza-MLN-4760 were similar to that of MLN-4760. Co-crystallization of the hACE2/F-MLN-4760 protein complex was performed for confirmation. Displacement ex2024-01-01T00:00:00Z2024 Dec2026-06-01T13:23:41.323Z2025-04-04T22:47:37.737ZS-EPMC115993133906680810.1007/s00259-024-06831-6