title: In vivo evaluation of gadolinium hydroxypyridonate chelates: initial experience as contrast media in magnetic resonance imaging.
abstract: The effect of ligand structure on the magnetic resonance (MR) imaging and biodistribution of six gadolinium (Gd) chelates based on a hydroxypyridonate-terephthalimide (HOPO-TAM) ligand design was investigated. Modifications to the molecular structure of the Gd-HOPO-TAM chelates (hydrophilicity and aromatic group substitution) significantly influence the efficacy of imaging and biodistribution. MR imaging was performed on female mice after intravenous (iv) injection of 100 micromol of Gd/kg of body weight of the different complexes. The biodistribution results indicate that the liver uptake of the complexes is enhanced by a short poly(ethyleneoxy) (PEO) chain, while blood pool localization is facilitated by a very long PEO chain. There is a direct correlation between the blood pool localization of the complexes and the signal intensity of blood vessels in the MRI. The imaging results are consistent with in vitro NMR measurements that indicate long PEO chains increase image enhancement capabilities in the presence of serum albumin.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: Marlon K
authors.initials: MK
authors.lastname: Thompson
authors.forename: Bernd
authors.initials: B
authors.lastname: Misselwitz
authors.forename: Luke S
authors.initials: LS
authors.lastname: Tso
authors.forename: Dan M J
authors.initials: DM
authors.lastname: Doble
authors.forename: Heribert
authors.initials: H
authors.lastname: Schmitt-Willich
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Raymond
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D005682:Gadolinium; D007094:Imides / Q000737:chemistry; D007275:Injections, Intravenous; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D009942:Organometallic Compounds / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D010795:Phthalic Acids / Q000737:chemistry; D013154:Spleen / Q000033:anatomy & histology / Q000378:metabolism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D007094:Imides; D009942:Organometallic Compounds; D010795:Phthalic Acids; D005682:Gadolinium