title: Comparison of dendrimer-based macromolecular contrast agents for dynamic micro-magnetic resonance lymphangiography.
abstract: Few methods are currently available to visualize the entire lymphatic system. A method known as micro-magnetic resonance lymphangiography (MRL), which employs a dendrimer-based MRI contrast agent (PAMAM-G8) and a clinical-grade 1.5T MRI instrument, was recently developed for use in mice. In the present study, three dendrimer-based MRI contrast agents (PAMAM-G8, DAB-G5, and PAMAM-G4) with different pharmacokinetic characteristics were compared to determine the best reagent to visualize the lymphatic system under physiological or pathological conditions. In addition, two established MRI contrast agents (Gadomer-17 and Gd-[DTPA]-dimeglumine (Magnevist)) were used as control agents. In experiments with mice, most of the deep lymphatic system was visualized by micro-MRL with all agents except Gd-[DTPA]-dimeglumine. PAMAM-G8 was best for visualizing lymphatic vessels, whereas DAB-G5 was better for visualizing lymph nodes. PAMAM-G4 was intermediate in character between PAMAM-G8 and DAB-G5, except in exhibiting a low background signal (especially in the liver). The lymphatic system was not clearly visualized with Gd-[DTPA]-dimeglumine; however, the lymph nodes were visualized with Gadomer-17, although not as well as with dendrimer-based agents. In conclusion, DAB-G5 and PAMAM-G4 can be used to identify lymph nodes and lymphatic vessels, respectively. Their rapid excretion makes these compounds potentially attractive for human use.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1374, 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: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.forename: Michael V
authors.initials: MV
authors.lastname: Knopp
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tagaya
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000818:Animals; D003287:Contrast Media; D050091:Dendrimers; D005682:Gadolinium; D019786:Gadolinium DTPA; D006801:Humans; D008206:Lymphatic Diseases / Q000175:diagnosis; D008208:Lymphatic System / Q000033:anatomy & histology*; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011073:Polyamines
chemical_list: D003287:Contrast Media; D050091:Dendrimers; D046911:Macromolecular Substances; C104700:PAMAM Starburst; D011073:Polyamines; C402765:gadomer 17; D005682:Gadolinium; D019786:Gadolinium DTPA