title: Preparation, characterization and in vivo assessment of Gd-albumin and Gd-dendrimer conjugates as intravascular contrast-enhancing agents for MRI.
abstract: We report in vivo and in vitro MRI properties of six gadolinium-dendrimer and gadolinium-albumin conjugates of derivatized acyclic diethylenetriamine-N,N',N',N″, N″-pentaacetic acid (1B4M) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (C-DOTA). The three albumin-based agents have comparable protein to chelate ratios (1:16-18) as well as molar relaxivity (8.8-10.4 mM(-1) s(-1)). The three dendrimer based agents have blood clearance half-lives ranging from 17 to 66 min while that of the three albumin-based agents are comparable to one another (40-47 min). The dynamic image obtained from use of the albumin conjugate based on the macrocycle (C-DOTA) showed a higher contrast compared to the remaining two albumin based agents. Our conclusion from all of the results is that the macrocyclic-based (DOTA) agents are more suitable than the acyclic-based (1B4M) agent for in vivo use based on their MRI properties combined with the kinetic inertness property associated with the more stable Gd(III) DOTA complex.
authors.affiliation: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892, United States.
authors.forename: Kido
authors.initials: K
authors.lastname: Nwe
authors.forename: Diane
authors.initials: D
authors.lastname: Milenic
authors.forename: L Henry
authors.initials: LH
authors.lastname: Bryant
authors.forename: Celeste A S
authors.initials: CA
authors.lastname: Regino
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D056831:Coordination Complexes / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D005260:Female; D005682:Gadolinium / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D007601:Jugular Veins / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging
chemical_list: D000418:Albumins; D003287:Contrast Media; D056831:Coordination Complexes; D050091:Dendrimers; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium