title: Novel liver macromolecular MR contrast agent with a polypropylenimine diaminobutyl dendrimer core: comparison to the vascular MR contrast agent with the polyamidoamine dendrimer core.
abstract: As MRI contrast agents, more hydrophobic molecules reportedly accumulate in the liver and thus are potentially useful as liver MRI contrast agents. In this study, a generation-4 polypropylenimine diaminobutane dendrimer (DAB-Am64), which is expected to be more hydrophobic than the generation-4 polyamidoamine dendrimer (PAMAM-G4D), was used to synthesize a conjugate with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M) [DAB-Am64-(1B4M-Gd)(64)] for complexing Gd(III) ions. This DAB conjugate quickly accumulated in the liver and its characteristics were studied and compared with those of a PAMAM conjugate [PAMAM-G4D-(1B4M-Gd)(64)], which is known to be a useful vascular MRI contrast agent, in regard to its availability as a liver MRI contrast agent. DAB-Am64-(1B4M-Gd)(64) accumulated significantly more in the liver and less in blood than PAMAM-G4D-(1B4M-Gd)(64) (P < 0.001). Contrast-enhanced MRI with DAB-Am64-(1B4M-Gd)(64) was able to homogeneously enhance liver parenchyma and visualize both portal and hepatic veins of 0.5 mm diameter in mice. In conclusion, DAB-Am64-(1B4M-Gd)(64) is a good candidate for a liver MRI contrast agent.
authors.affiliation: Hitachi Medical Co. Chaired Department of Diagnostic and Interventional Imagiology, Kyoto University, Graduate School of Medicine, Sakyo, Kyoto, Japan. hisataka@kuhp.kyoto-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Kawamoto
authors.forename: T
authors.initials: T
authors.lastname: Saga
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Hiraga
authors.forename: T
authors.initials: T
authors.lastname: Ishimori
authors.forename: Y
authors.initials: Y
authors.lastname: Akita
authors.forename: M H
authors.initials: MH
authors.lastname: Mamede
authors.forename: J
authors.initials: J
authors.lastname: Konishi
authors.forename: K
authors.initials: K
authors.lastname: Togashi
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000493:pharmacokinetics*; D050091:Dendrimers; D019786:Gadolinium DTPA / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D011073:Polyamines / Q000493:pharmacokinetics*
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; C430743:DAB-Am64-(1B4M-Gd)64; D050091:Dendrimers; D046911:Macromolecular Substances; C104700:PAMAM Starburst; D011073:Polyamines; D019786:Gadolinium DTPA