title: The Gd3+ complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(p-isothiocyanatoanilide) conjugated to inulin: a potential stable macromolecular contrast agent for MRI.
abstract: Reaction of DOTA-NCSA [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(p-isothiocyanatoanilide)] with O-(aminopropyl)inulin (degree of polymerization 25) provided a chelate that formed a kinetically extremely stable Gd(3+) complex. No transmetalation was observed with Zn(2+). The conjugate has a relaxivity of 21.7 s(-1) mM(-1) at 20 MHz and 37 °C, and each molecule of the inulin carries on average 35 Gd(3+) ions. The parameters governing the relaxivity of this material and of a low-molecular-weight model compound prepared by conjugation of DOTA-NCSA and propylamine were evaluated by investigation of their water (1)H longitudinal relaxation rate enhancements at different magnetic fields (NMRD) and by studying variable temperature (17)O NMR data. The high relaxivity of the inulin conjugate can be ascribed to the efficient slowing down of the molecular tumbling by this carrier. The rotational correlation time at 37 °C of this material is 1460 ps, whereas that of the model compound is 84 ps. Furthermore, both complexes do not interact significantly with human serum albumin, as shown by their NMRD profiles, and do not undergo transmetallation by zinc ions. The inulin conjugate thus has potential for application as a contrast agent for MRI, particularly as a blood pool agent.
authors.affiliation: Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium.
authors.forename: Luigi
authors.initials: L
authors.lastname: Granato
authors.forename: Sophie
authors.initials: S
authors.lastname: Laurent
authors.forename: Luce
authors.initials: L
authors.lastname: Vander Elst
authors.forename: Kristina
authors.initials: K
authors.lastname: Djanashvili
authors.forename: Joop A
authors.initials: JA
authors.lastname: Peters
authors.forename: Robert N
authors.initials: RN
authors.lastname: Muller
mesh_terms: D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D007444:Inulin / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry; D014316:Tritium / Q000737:chemistry
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D006571:Heterocyclic Compounds; C115515:O-(aminopropyl)inulin; D009942:Organometallic Compounds; D012709:Serum Albumin; D014316:Tritium; D007444:Inulin; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D013890:Thiourea