title: Tuning phenols with Intra-Molecular bond Shifted HYdrogens (IM-SHY) as diaCEST MRI contrast agents.
abstract: The optimal exchange properties for chemical exchange saturation transfer (CEST) contrast agents on 3 T clinical scanners were characterized using continuous wave saturation transfer, and it was demonstrated that the exchangeable protons in phenols can be tuned to reach these criteria through proper ring substitution. Systematic modification allows the chemical shift of the exchangeable protons to be positioned between 4.8 to 12 ppm from water and enables adjustment of the proton exchange rate to maximize CEST contrast at these shifts. In particular, 44 hydrogen-bonded phenols are investigated for their potential as CEST MRI contrast agents and the stereoelectronic effects on their CEST properties are summarized. Furthermore, a pair of compounds, 2,5-dihydroxyterephthalic acid and 4,6-dihydroxyisophthalic acid, were identified which produce the highest sensitivity through incorporating two exchangeable protons per ring.
authors.affiliation: The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, 991 N. Broadway Baltimore, MD 21287 (USA).
authors.forename: Xing
authors.initials: X
authors.lastname: Yang
authors.forename: Nirbhay N
authors.initials: NN
authors.lastname: Yadav
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Song
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Ray Banerjee
authors.forename: Hannah
authors.initials: H
authors.lastname: Edelman
authors.forename: Il
authors.initials: I
authors.lastname: Minn
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zijl
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
mesh_terms: D003287:Contrast Media / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D006860:Hydrogen Bonding; D008279:Magnetic Resonance Imaging; D010636:Phenols / Q000737:chemistry*; D010795:Phthalic Acids / Q000737:chemistry*
chemical_list: C000599921:2,5-dihydroxyterephthalic acid; C000599922:4,6-dihydroxyisophthalic acid; D003287:Contrast Media; D010636:Phenols; D010795:Phthalic Acids; D006859:Hydrogen
keywords: chemical exchange saturation transfer; imaging agents; magnetic resonance imaging; medicinal chemistry; molecular imaging