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Comparative Study
. 2010 Aug 15;18(16):5925-31.
doi: 10.1016/j.bmc.2010.06.086. Epub 2010 Jul 8.

Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates

K Nwe  1 , M Bernardo, C A S Regino, M Williams, M W Brechbiel
Affiliations
Comparative Study

Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates

K Nwe et al. Bioorg Med Chem. .

Abstract

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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Figures

Figure 1
Figure 1
Synthetic scheme for G4-(C-DOTA-Gd)28 conjugate.
Figure 2
Figure 2
Molar relaxivity plots of G4-(C-DOTA-Gd)28 (▲; 29.5 mM−1s−1), G4-(1B4M-DTPA-Gd)30 (■; 26.9 mM−1s−1) and Magnevist (♦; 4.2 mM−1s−1).
Figure 3
Figure 3
Average blood clearance rates measured at the jugular vein of G4-(1B4M-DTPA-Gd)30 and G4-(C-DOTA-Gd)28.
Figure 4
Figure 4
Dynamic MRI of mice injected with 0.015 mmol/Kg of G4-(C-DOTA-Gd)28 (above) and G4-(1B4M-DTPAGd)30 (below). All images were acquired at 16–23 min post-injection.
Figure 4
Figure 4
Dynamic MRI of mice injected with 0.015 mmol/Kg of G4-(C-DOTA-Gd)28 (above) and G4-(1B4M-DTPAGd)30 (below). All images were acquired at 16–23 min post-injection.
Figure 5
Figure 5
MR images of the left kidney obtained prior to injection of agents (a) and 20 min after injection of G4-(1B4M-DTPA-Gd)30 (b) and G4-(C-DOTA-Gd)28 (c).
Figure 6
Figure 6
Structures of (C-DOTA-Gd)−1 (left) vs. (1B4M-DTPA-Gd)−2 (right).
See this image and copyright information in PMC

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