title: Iron(II) PARACEST MRI contrast agents.
abstract: The first examples of Fe(II) PARACEST magnetic resonance contrast agents are reported (PARACEST = paramagnetic chemical exchange saturation transfer). The iron(II) complexes contain a macrocyclic ligand, either 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane (L1) or 1,4,7-tris[(5-amino-6-methyl-2-pyridyl)methyl]-1,4,7-triazacyclononane (L2). The macrocycles bind Fe(II) in aqueous solution with formation constants of log K = 13.5 and 19.2, respectively, and maintain the Fe(II) state in the presence of air. These complexes each contain six exchangeable protons for CEST which are amide protons in [Fe(L1)](2+) or amino protons in [Fe(L2)](2+). The CEST peak for the [Fe(L1)](2+) amide protons is at 69 ppm downfield of the bulk water resonance whereas the CEST peak for the [Fe(L2)](2+) amine protons is at 6 ppm downfield of bulk water. CEST imaging using a MRI scanner shows that the CEST effect can be observed in solutions containing low millimolar concentrations of complex at neutral pH, 100 mM NaCl, 20 mM buffer at 25 °C or 37 °C.
authors.affiliation: Department of Chemistry, University at Buffalo, State University of New York, Amherst, New York 14260, USA.
authors.forename: Sarina J
authors.initials: SJ
authors.lastname: Dorazio
authors.forename: Pavel B
authors.initials: PB
authors.lastname: Tsitovich
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Siters
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Spernyak
authors.forename: Janet R
authors.initials: JR
authors.lastname: Morrow
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry*; D008024:Ligands; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D019047:Phantoms, Imaging
chemical_list: D003287:Contrast Media; D005296:Ferrous Compounds; D008024:Ligands; D047028:Macrocyclic Compounds