title: Dissociation of gadolinium chelates in mice: relationship to chemical characteristics.
abstract: Tissue distributions of seven 153Gd-labeled Gd chelates were determined at five residence intervals (5 min to 14 days) following intravenous administration of 0.4 mmol/kg to mice. Relationships were sought among physicochemical parameters: thermodynamic and conditional (pH 7.4) equilibrium stability constants (log K and log K'), acid dissociation rate constants (k(obs)), lipophilicity (log P), overall charge, and size (molecular weight). Size and lipophilicity did not correlate with tissue distributions. There were possible correlations between anionic charge and rapid, early renal excretion and between stability constants and long-term residual Gd deposition. Strong correlations (r greater than 0.99) were found between acid dissociation rates and long-term deposition of Gd in the whole body, liver, and femur. This is attributed to dissociation of Gd from the chelates in vivo. Acid dissociation rates may be useful in predicting dissociation of Gd from chelates in vivo.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Contrast Media Research Department, New Brunswick, NJ 08903.
authors.forename: P
authors.initials: P
authors.lastname: Wedeking
authors.forename: K
authors.initials: K
authors.lastname: Kumar
authors.forename: M F
authors.initials: MF
authors.lastname: Tweedle
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000493:pharmacokinetics*; D004492:Edetic Acid / Q000493:pharmacokinetics; D005682:Gadolinium / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; C041365:gadolinium EDTA; D004369:Pentetic Acid; C064925:gadodiamide; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D004492:Edetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA