title: Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as 'sponges' of Gd3+ ions.
abstract: MR-labeling of cells may be carried out by adding a Gd-based contrast agent to the incubation media. The amount of gadolinium internalized in HTC and C6 cells upon incubation with Gd-DTPA-BMA is circa one order of magnitude higher than those found with Gd-DTPA, Gd-DOTA and Gd-HPDO3A, respectively. The comparison of relaxometric and mass spectrometry determinations allows us to establish that only a minor fraction of intact Gd-DTPA-BMA is internalized into the cells. Moreover the binding/uptake behavior shown by Gd-DTPA-BMA resembles that found when GdCl(3) is added to the incubation medium. We suggest that the lower stability of Gd-DTPA-BMA is responsible for a shift in the dissociation equilibrium that results in the net transfer of Gd(3+) ions on the cell membrane followed by a slower internalization process. The transmetallation process is mediated by components of the incubation media, among which a dominant role is represented by phosphate anions. The uptake of Gd(3+) ions is clearly reflected in the drastic decrease of cell viability observed for cells labeled with Gd-DTPA-BMA.
authors.affiliation: CRM Bracco Imaging S.p.A. c/o Bioindustry Park Canavese Via Ribes 5, Colleretto Giacosa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cabella
authors.forename: S Geninatti
authors.initials: SG
authors.lastname: Crich
authors.forename: D
authors.initials: D
authors.lastname: Corpillo
authors.forename: A
authors.initials: A
authors.lastname: Barge
authors.forename: C
authors.initials: C
authors.lastname: Ghirelli
authors.forename: E
authors.initials: E
authors.lastname: Bruno
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: F
authors.initials: F
authors.lastname: Uggeri
authors.forename: S
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005682:Gadolinium / Q000737:chemistry* / Q000493:pharmacokinetics*; D007477:Ions / Q000493:pharmacokinetics; D013058:Mass Spectrometry; D008954:Models, Biological; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D051381:Rats; D013194:Staining and Labeling / Q000379:methods*; D013816:Thermodynamics; D014407:Tumor Cells, Cultured
chemical_list: D003287:Contrast Media; D007477:Ions; D009942:Organometallic Compounds; D005682:Gadolinium; C038958:gadolinium chloride