title: Amplifying the sensitivity of zinc(II) responsive MRI contrast agents by altering water exchange rates.
abstract: Given the known water exchange rate limitations of a previously reported Zn(II)-sensitive MRI contrast agent, GdDOTA-diBPEN, new structural targets were rationally designed to increase the rate of water exchange to improve MRI detection sensitivity. These new sensors exhibit fine-tuned water exchange properties and, depending on the individual structure, demonstrate significantly improved longitudinal relaxivities (r1). Two sensors in particular demonstrate optimized parameters and, therefore, show exceptionally high longitudinal relaxivities of about 50 mM(-1) s(-1) upon binding to Zn(II) and human serum albumin (HSA). This value demonstrates a 3-fold increase in r1 compared to that displayed by the original sensor, GdDOTA-diBPEN. In addition, this study provides important insights into the interplay between structural modifications, water exchange rate, and kinetic stability properties of the sensors. The new high relaxivity agents were used to successfully image Zn(II) release from the mouse pancreas in vivo during glucose stimulated insulin secretion.
authors.affiliation: Department of Chemistry, University of Texas at Dallas , P.O. Box 830668, Richardson, Texas 75083, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Chemistry, University of Texas at Dallas , P.O. Box 830668, Richardson, Texas 75083, United States.
authors.forename: André F
authors.initials: AF
authors.lastname: Martins
authors.affiliation: Advanced Imaging Research Center, The University of Texas , Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Preihs
authors.affiliation: Advanced Imaging Research Center, The University of Texas , Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
authors.forename: Veronica
authors.initials: V
authors.lastname: Clavijo Jordan
authors.affiliation: Advanced Imaging Research Center, The University of Texas , Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
authors.forename: Sara
authors.initials: S
authors.lastname: Chirayil
authors.affiliation: Department of Chemistry, University of Texas at Dallas , P.O. Box 830668, Richardson, Texas 75083, United States.
authors.forename: Piyu
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Advanced Imaging Research Center, The University of Texas , Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
authors.forename: Yunkou
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Advanced Imaging Research Center, The University of Texas , Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
authors.forename: Khaled
authors.initials: K
authors.lastname: Nasr
authors.affiliation: Department of Chemistry, University of Texas at Dallas , P.O. Box 830668, Richardson, Texas 75083, United States.|Macrocyclics, Inc. , 1309 Record Crossing, Dallas, Texas 75235, United States.
authors.forename: Garry E
authors.initials: GE
authors.lastname: Kiefer
authors.affiliation: Department of Chemistry, University of Texas at Dallas , P.O. Box 830668, Richardson, Texas 75083, United States.|Advanced Imaging Research Center, The University of Texas , Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010179:Pancreas / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014867:Water / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; C000609391:GdDOTA-diBPEN diamide; D006573:Heterocyclic Compounds, 1-Ring; D007328:Insulin; D012709:Serum Albumin; D014867:Water; D005947:Glucose; D015032:Zinc