title: Breaking the Barrier to Slow Water Exchange Rates for Optimal Magnetic Resonance Detection of paraCEST Agents.
abstract: EuDOTA-tetraamide complexes as paraCEST agents offer an attractive platform for designing biological sensors and responsive agents. The early versions of these agents showed low sensitivity at temperature and power levels suitable for in vivo applications partly due to non-optimal water exchange rates. Here we report two new EuDOTA derivatives having glutamyl-phosphonate side arms that display the slowest water exchange rates of any other paraCEST agent reported so far. The advantages of such systems are demonstrated experimentally both in vitro and in vivo and DFT calculations were performed to help understand the physical-chemical reasons for this interesting behavior.
authors.affiliation: Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.
authors.forename: W Shirangi
authors.initials: WS
authors.lastname: Fernando
authors.affiliation: Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.
authors.forename: André F
authors.initials: AF
authors.lastname: Martins
authors.affiliation: Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.
authors.forename: Piyu
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.
authors.forename: Yunkou
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.|Macrocyclics, Incorporated, Dallas, Texas 75235, United States.
authors.forename: Garry E
authors.initials: GE
authors.lastname: Kiefer
authors.affiliation: Grupo QUICOOR, Centro de Investigaciones Científicas Avanzadas (CICA) and Departamento de Química Fundamental, Universidade da Coruña , Campus da Zapateira, Rúa da Fraga 10, 15008 A Coruña, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Platas-Iglesias
authors.affiliation: Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.|Advanced Imaging Research Center, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
mesh_terms: D000818:Animals; D003287:Contrast Media; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D008958:Models, Molecular; D066244:Proton Magnetic Resonance Spectroscopy; D013057:Spectrum Analysis / Q000379:methods; D014867:Water / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D014867:Water