title: The NiCEST approach: nickel(II) paraCEST MRI contrast agents.
abstract: Paramagnetic Ni(II) complexes are shown here to form paraCEST MRI contrast agents (paraCEST = paramagnetic chemical exchange saturation transfer; NiCEST = Ni(II) based CEST agents). Three azamacrocycles with amide pendent groups bind Ni(II) to form stable NiCEST contrast agents including 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane (L1), 1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane (L2), and 7,13-bis(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (L3). [Ni(L3)](2+), [Ni(L1)](2+), and [Ni(L2)](2+) have CEST peaks attributed to amide protons that are shifted 72, 76, and 76 ppm from the bulk water resonance, respectively. Both CEST MR images and CEST spectroscopy show that [Ni(L3)](2+) has the largest CEST effect in 100 mM NaCl, 20 mM HEPES pH 7.4 at 37 °C. This larger CEST effect is attributed to the sharper proton resonances of the complex which arise from a rigid structure and low relaxivity.
authors.affiliation: Department of Chemistry, University at Buffalo, State University of New York, Amherst, 14260, United States.
authors.forename: Abiola O
authors.initials: AO
authors.lastname: Olatunde
authors.forename: Sarina J
authors.initials: SJ
authors.lastname: Dorazio
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*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D009532:Nickel