Poly(amidoamine) dendrimer based MRI contrast agents exhibiting enhanced relaxivities derived via metal preligation techniques.
This report presents the preparation and characterization of three [Gd-C-DOTA](-1)-dendrimer assemblies by way of analysis, NMRD spectroscopy, and photon correlation spectroscopy (PCS). The metal-ligand chelates were preformed in alcohol media prior to conjugation to generation 4, 5, and 6 PAMAM dendrimers. The dendrimer-based agents were purified by Sephadex G-25 column chromatography. The combustion analysis, SE-HPLC, and UV-vis data indicated chelate to dendrimer ratios of 28:1, 61:1 and 115:1, respectively. Molar relaxivity measured at pH 7.4, 22 degrees C, and 3 T (29.6, 49.8, and 89.1 mM(-1) s(-1)) indicated the viability of conjugates as MRI contrast agents. 1/T(1) NMRD profiles were measured at 23 degrees C and indicated that at 22 MHz the 1/T(1) reached a plateau at 60, 85, and 140 mM(-1) s(-1) for the generation 4, 5, and 6 dendrimer conjugates, respectively. The PCS data showed the respective sizes of 5.2, 6.5, and 7.8 nm for G-4, 5, and 6 conjugates.
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Kido
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Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Bryant
L Henry
LH
Brechbiel
Martin W
MW
D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D002614:Chelating Agents; D003287:Contrast Media; D050091:Dendrimers; D006571:Heterocyclic Compounds; D008024:Ligands; D009942:Organometallic Compounds; C531249:Poly(amidoamine); D011073:Polyamines; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium
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