Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as 'sponges' of Gd3+ ions.
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.
Cabella
C
C
CRM Bracco Imaging S.p.A. c/o Bioindustry Park Canavese Via Ribes 5, Colleretto Giacosa, Italy.
Crich
S Geninatti
SG
Corpillo
D
D
Barge
A
A
Ghirelli
C
C
Bruno
E
E
Lorusso
V
V
Uggeri
F
F
Aime
S
S
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
D003287:Contrast Media; D007477:Ions; D009942:Organometallic Compounds; D005682:Gadolinium; C038958:gadolinium chloride