title: Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores.
abstract: Large macromolecular MRI contrast agents with albumin or dendrimer cores are useful for imaging blood vessels. However, their prolonged retention is a major limitation for clinical use. Although smaller dendrimer-based MRI contrast agents are more quickly excreted by the kidneys, they are also able to visualize vascular structures better than Gd-DTPA due to less extravasation. Additionally, unlike Gd-DTPA, they transiently accumulate in renal tubules and thus also can be used to visualize renal structural and functional damage. However, these dendrimer agents are retained in the body for a prolonged time. The purpose of this study was to obtain information from which a macromolecular dendrimer-based MRI contrast agents feasible for use in further clinical studies could be chosen. Six small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole-body retention, and dynamic MRI were evaluated in mice to determine an optimal agent in comparison to Gd-[DTPA]-dimeglumine. Diaminobutane (DAB) dendrimer-based agents cleared more rapidly from the body than polyamidoamine (PAMAM) dendrimer-based agents with the same numbers of branches. Smaller dendrimer conjugates were more rapidly excreted from the body than the larger dendrimer conjugates. Since PAMAM-G2, DAB-G3, and DAB-G2 dendrimer-based contrast agents showed relatively rapid excretion, these three conjugates might be acceptable for use in further clinical applications.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Kobayash@mail.nih.gov
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Satomi
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
authors.forename: Henry L
authors.initials: HL
authors.lastname: Bryant
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D050091:Dendrimers; D005260:Female; D005682:Gadolinium; D019786:Gadolinium DTPA / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D011073:Polyamines / Q000737:chemistry; D011786:Quality Control; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D005682:Gadolinium; D019786:Gadolinium DTPA