title: Chemical Exchange Saturation Transfer (CEST) Agents: Quantum Chemistry and MRI.
abstract: Diamagnetic chemical exchange saturation transfer (CEST) contrast agents offer an alternative to Gd(3+) -based contrast agents for MRI. They are characterized by containing protons that can rapidly exchange with water and it is advantageous to have these protons resonate in a spectral window that is far removed from water. Herein, we report the first results of DFT calculations of the (1) H nuclear magnetic shieldings in 41 CEST agents, finding that the experimental shifts can be well predicted (R(2) =0.882). We tested a subset of compounds with the best MRI properties for toxicity and for activity as uncouplers, then obtained mice kidney CEST MRI images for three of the most promising leads finding 16 (2,4-dihydroxybenzoic acid) to be one of the most promising CEST MRI contrast agents to date. Overall, the results are of interest since they show that (1) H NMR shifts for CEST agents-charged species-can be well predicted, and that several leads have low toxicity and yield good in vivo MR images.
authors.affiliation: Department of Chemistry University of Illinois at Urbana Champaign, 600 South Mathews Urbana, IL 61801 (USA).
authors.forename: Jikun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Chemistry University of Illinois at Urbana Champaign, 600 South Mathews Urbana, IL 61801 (USA).
authors.forename: Xinxin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Chemistry University of Illinois at Urbana Champaign, 600 South Mathews Urbana, IL 61801 (USA).
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, 991 N. Broadway Baltimore, Maryland 21287 (USA).
authors.forename: Nikita
authors.initials: N
authors.lastname: Oskolkov
authors.affiliation: Department of Chemistry University of Illinois at Urbana Champaign, 600 South Mathews Urbana, IL 61801 (USA).
authors.forename: Tianhui
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Chemistry University of Illinois at Urbana Champaign, 600 South Mathews Urbana, IL 61801 (USA).
authors.forename: Boo Kyung
authors.initials: BK
authors.lastname: Kim
authors.affiliation: Department of Chemistry University of Illinois at Urbana Champaign, 600 South Mathews Urbana, IL 61801 (USA).
authors.forename: Noman
authors.initials: N
authors.lastname: Baig
authors.affiliation: The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, 991 N. Broadway Baltimore, Maryland 21287 (USA). mtmcmaho@gmail.com.|F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21287 (USA). mtmcmaho@gmail.com.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
authors.affiliation: Department of Chemistry University of Illinois at Urbana Champaign, 600 South Mathews Urbana, IL 61801 (USA). eoldfiel@illinois.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Oldfield
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D062385:Hydroxybenzoates / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011789:Quantum Theory
chemical_list: D003287:Contrast Media; D062385:Hydroxybenzoates; D005682:Gadolinium; C017704:beta-resorcylic acid
keywords: CEST MRI; NMR spectroscopy; contrast agents; density functional calculations; salicylate