title: Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core: accelerated renal excretion with coinjection of lysine.
abstract: One of the major limitations to macromolecular MRI contrast agents (MRI-CAs) is their slow clearance and associated decreased excretion of gadolinium (Gd(III)). The effect of coinjecting lysine to accelerate renal excretion of a macromolecular MRI-CA (generation-4 PAMAM dendrimer (G4D-(1B4M-Gd)64)) was investigated. The biodistribution and urine and fecal excretion in athymic mice was evaluated with and without lysine coinjection. 3D-dynamic-micro-MRI with G4D-(1B4M-Gd)64 was obtained with and without lysine coinjection, and the serial signal intensity (SI) change in the blood and organs was evaluated. When lysine was coinjected, urinary excretion of G4D-(1B4M-Gd)64 increased 5.4-fold compared to that without lysine, resulting in decreased renal accumulation of G4D-(1B4M-Gd)64 from 150% to 40% injected dose per gram (P < 0.001). On dynamic MRI with G4D-(1B4M-Gd)64, when lysine was coinjected, the kidney-to-blood SI ratio was significantly lower than that obtained without lysine (P < 0.001). When lysine was coinjected, the G4D-(1B4M-Gd)64 was excreted from the kidney intact.
authors.affiliation: Hitachi Medical Co. Chaired Department of Diagnostic and Interventional Imaging, Kyoto University, Kyoto, Japan. hisataka@kuhp.kyoto-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Kawamoto
authors.forename: T
authors.initials: T
authors.lastname: Saga
authors.forename: A
authors.initials: A
authors.lastname: Hiraga
authors.forename: T
authors.initials: T
authors.lastname: Ishimori
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; D003287:Contrast Media / Q000493:pharmacokinetics*; D050091:Dendrimers; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D008239:Lysine / Q000494:pharmacology*; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008657:Metabolic Clearance Rate / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D011073:Polyamines / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D008239:Lysine