title: Reporter protein-targeted probes for magnetic resonance imaging.
abstract: Contrast agents for magnetic resonance imaging are frequently employed as experimental and clinical probes. Drawbacks include low signal sensitivity, fast clearance, and nonspecificity that limit efficacy in experimental imaging. In order to create a bioresponsive MR contrast agent, a series of four Gd(III) complexes targeted to the HaloTag reporter were designed and synthesized. HaloTag is unique among reporter proteins for its specificity, versatility, and the covalent interaction between substrate and protein. In similar systems, these properties produce prolonged in vivo lifetimes and extended imaging opportunities for contrast agents, longer rotational correlation times, and increases in relaxivity (r(1)) upon binding to the HaloTag protein. In this work we report a new MR contrast probe, 2CHTGd, which forms a covalent bond with its target protein and results in a dramatic increase in sensitivity. A 6-fold increase in r(1), from 3.8 to 22 mM(-1) s(-1), is observed upon 2CHTGd binding to the target protein. This probe was designed for use with the HaloTag protein system which allows for a variety of substrates (specific for MRI, florescence, or protein purification applications) to be used with the same reporter.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA.
authors.forename: Renee C
authors.initials: RC
authors.lastname: Strauch
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mastarone
authors.forename: Preeti A
authors.initials: PA
authors.lastname: Sukerkar
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ipsaro
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meade
mesh_terms: D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry; D008164:Luminescent Proteins / Q000032:analysis / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D003287:Contrast Media; D008164:Luminescent Proteins; D009942:Organometallic Compounds; D005682:Gadolinium