title: Effective encapsulation of a new cationic gadolinium chelate into apoferritin and its evaluation as an MRI contrast agent.
abstract: Gd-Me(2)DO2A with a T(1) proton relaxivity twice as high as that of commercial Gd-DOTA was newly designed and synthesized. Me(2)DO2A kept its high association property with gadolinium ions (Gd(3+)), and the Gd-Me(2)DO2A was efficiently encapsulated into the apoferritin cavity to further enhance the T(1) relaxivity as much as 10-fold higher than Gd-DOTA on a Gd basis. The high T(1) relaxivity was attained by (i) increased accessibility of water molecules to Gd(3+) ions in the chelate and (ii) macromolecular effect of the encapsulation. By the surface modification of apoferritin with dextran, in vivo blood clearance time of apoferritin could be prolonged. Magnetic resonance imaging of tumor-bearing mice showed that the apoferritin contrast agent accomplished tumor detection effectively as a bright signal as a result of the enhanced permeation and retention effect. Single-dose toxicity test showed no serious side effects. The apoferritin-encapsulated Gd is therefore a possible candidate for a new magnetic resonance imaging contrast agent.
authors.affiliation: Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku-Katsura, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Makino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Okada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Hiroo
authors.initials: H
authors.lastname: Amano
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000737:chemistry*; D002412:Cations; D002614:Chelating Agents / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis*; D009942:Organometallic Compounds / Q000737:chemistry
chemical_list: D002412:Cations; D002614:Chelating Agents; D003287:Contrast Media; D056831:Coordination Complexes; C569625:Gd-Me(2)DO2A; D006571:Heterocyclic Compounds; D053769:Nanocapsules; D009942:Organometallic Compounds; D001052:Apoferritins; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate