Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates.
In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N',N',N'',N''-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex(R) G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1, respectively. Molar relaxivity measured at pH 7.4, 22 degrees C, and 3T are comparable (29.5 vs 26.9 mM(-1)s(-1)), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t(1/2)=16 vs 29 min). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties.
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Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Bernardo
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M
Regino
C A S
CA
Williams
M
M
Brechbiel
M W
MW
D000818:Animals; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000737:chemistry* / Q000493:pharmacokinetics
D003287:Contrast Media; D050091:Dendrimers; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D004369:Pentetic Acid; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate