Phosphonate-modified GdDTPA complexes. I. NMRD study of the solution behavior of new tissue-specific contrast agents.
NMRD profiles, the magnetic field dependence of the water proton longitudinal relaxation rates, have been acquired for two new diphosphonate-modified GdDTPA complexes currently under evaluation as relaxation agents for the MRI detection of soft-tissue calcifications. Fresh dilute solutions show profiles identical to that of unmodified GdDTPA, which remain unchanged for up to 9 weeks. Solutions containing Gd species at MRI significant concentrations, 100 to 500 mM, show the presence of oligomers (n = 5 or more) upon aging, with much higher high-field relaxivities. Aggregation is attributed to the interactions between a gadolinium center and the phosphonate terminus of a neighboring molecule, and is prevented by esterification of the phosphonate terminus. Oligomers are also easily disrupted by dilution with phosphate-buffered saline, where the exogenous phosphate ions compete with the phosphonate. Other nucleophiles such as are present in protein side chains of bovine serum albumin also compete with the phosphonate in these associations, the result being species with even higher relaxivities.
Adzamli
I K
IK
Department of Radiology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Blau
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D003287:Contrast Media / Q000737:chemistry; D004164:Diphosphonates / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry*; D000077268:Pamidronate; D004369:Pentetic Acid / Q000737:chemistry*
D003287:Contrast Media; D004164:Diphosphonates; D009942:Organometallic Compounds; D063065:Organophosphonates; C058568:aminobutane bisphosphonate; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA; D000077268:Pamidronate