title: Water-soluble gadofullerenes: toward high-relaxivity, pH-responsive MRI contrast agents.
abstract: The water-soluble endohedral gadofullerene derivatives, Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH)(2)](10), have been characterized with regard to their MRI contrast agent properties. Water-proton relaxivities have been measured in aqueous solution at variable temperature (278-335 K), and for the first time for gadofullerenes, relaxivities as a function of magnetic field (5 x 10(-4) to 9.4 T; NMRD profiles) are also reported. Both compounds show relaxivity maxima at high magnetic fields (30-60 MHz) with a maximum relaxivity of 10.4 mM(-1) s(-1) for Gd@C(60)[C(COOH)(2)](10) and 38.5 mM(-1) s(-1) for Gd@C(60)(OH)(x) at 299 K. Variable-temperature, transverse and longitudinal (17)O relaxation rates, and chemical shifts have been measured at three magnetic fields (B = 1.41, 4.7, and 9.4 T), and the results point exclusively to an outer sphere relaxation mechanism. The NMRD profiles have been analyzed in terms of slow rotational motion with a long rotational correlation time calculated to be tau(R)(298) = 2.6 ns. The proton exchange rate obtained for Gd@C(60)[C(COOH)(2)](10) is k(ex)(298) = 1.4 x 10(7) s(-1) which is consistent with the exchange rate previously determined for malonic acid. The proton relaxivities for both gadofullerene derivatives increase strongly with decreasing pH (pH: 3-12). This behavior results from a pH-dependent aggregation of Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH)(2)](10), which has been characterized by dynamic light scattering measurements. The pH dependency of the proton relaxivities makes these gadofullerene derivatives prime candidates for pH-responsive MRI contrast agent applications.
authors.affiliation: Laboratoire de Chimie Inorganique et Bioinorganique, Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH, CH-1015 Lausanne, Switzerland. eva.jakabtoth@epfl.ch
authors.forename: Eva
authors.initials: E
authors.lastname: Tóth
authors.forename: Robert D
authors.initials: RD
authors.lastname: Bolskar
authors.forename: Alain
authors.initials: A
authors.lastname: Borel
authors.forename: Gabriel
authors.initials: G
authors.lastname: González
authors.forename: Lothar
authors.initials: L
authors.lastname: Helm
authors.forename: André E
authors.initials: AE
authors.lastname: Merbach
authors.forename: Balaji
authors.initials: B
authors.lastname: Sitharaman
authors.forename: Lon J
authors.initials: LJ
authors.lastname: Wilson
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D037741:Fullerenes / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000737:chemistry*; D010103:Oxygen Isotopes; D011522:Protons; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D003287:Contrast Media; D037741:Fullerenes; D009942:Organometallic Compounds; D010103:Oxygen Isotopes; D011522:Protons; D014867:Water; D005682:Gadolinium; C069837:fullerene C60