title: Targeting radiopharmaceuticals: comparative biodistribution studies of gallium and indium complexes of multidentate ligands.
abstract: New multidentate ligands with structures similar to N,N'-bis[2-hydroxybenzyl]ethylenediamine-N,N'-diacetic acid (HBED) and N,N'-bis(pyridoxyl)ethylenediamine-N,N'-diacetic acid (PLED) were synthesized. The in vitro lipophilicity, electrophoretic behavior, and the in vitro biodistribution were studied for the 111In- and 67, 68Ga-complexes of N,N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine-N,N'-diacetic acid (Me4HBED); N,N'-bis(5-t-butyl-2-hydroxy-3-methylbenzyl)ethylenediamine-N,N'-diac eti c acid (t-butyl HBED); N,N'-bis[2-hydroxy-5-sulfobenzyl)ethylenediamine-N,N'-diacetic acid (SHBED); N,N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine-N-(2-hydroxyethyl) -N'-acetic acid (HBMA); and N,N'-bis(5-deoxypyridoxyl)ethylenediamine-N,N'-diacetic acid (DPLED). The biodistribution of the radiometal complexes were carried out in rats and an imaging study was performed in a non-human primate. The rapid clearance of the lipophilic complexes from blood and through the hepatobiliary system was easily demonstrated; as well, the hydrophilic complexes were cleared rapidly through the urinary tract. Positron emission tomographic images were generated from a study in a primate after administration of 68Ga-t-butyl HBED. These images well demonstrate the efficient liver accumulation and rapid hepatobiliary clearance (less than 1 h) and well differentiate images of the liver and gall bladder.
authors.affiliation: Edward Malinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110.
authors.forename: C J
authors.initials: CJ
authors.lastname: Mathias
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Sun
authors.forename: M J
authors.initials: MJ
authors.lastname: Welch
authors.forename: M A
authors.initials: MA
authors.lastname: Green
authors.forename: J A
authors.initials: JA
authors.lastname: Thomas
authors.forename: K R
authors.initials: KR
authors.lastname: Wade
authors.forename: A E
authors.initials: AE
authors.lastname: Martell
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics*; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008024:Ligands; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D002614:Chelating Agents; D005710:Gallium Radioisotopes; D007205:Indium Radioisotopes; D008024:Ligands; D009942:Organometallic Compounds