959153-72-1Relevant articles and documents
Comparison of MRI Properties between Multimeric DOTAGA and DO3A Gadolinium-Dendron Conjugates
Ndiaye, Maleotane,Malytskyi, Volodymyr,Vangijzegem, Thomas,Sauvage, Félix,Wels, Mike,Cadiou, Cyril,Moreau, Juliette,Henoumont, Céline,Boutry, Sébastien,Muller, Robert N.,Harakat, Dominique,Smedt, Stefaan De,Laurent, Sophie,Chuburu, Fran?oise
, p. 12798 - 12808 (2019)
The inherent lack of sensitivity of MRI needs the development of new Gd contrast agents in order to extend the application of this technique to cellular imaging. For this purpose, two multimeric MR contrast agents obtained by peptidic coupling between an amido amine dendron and GdDOTAGA chelates (premetalation strategy, G1-4GdDOTAGA) or DO3A derivatives which then were postmetalated (G1-4GdDO3A) have been prepared. By comparison to the monomers, an increase of longitudinal relaxivity has been observed for both structures. Especially for G1-4GdDO3A, a marked increase is observed between 20 and 60 MHz. This structure differs from G1-4GdDOTAGA by an increased rigidity due to the aromatic linker between each chelate and the organic framework. This has the effect of limiting local rotational movements, which has a positive impact on relaxivity.
Synthesis and Relaxometric Characterization of New Poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) Dendrons Gd-Based Contrast Agents and Their in Vivo Study by Using the Dynamic Contrast-Enhanced MRI Technique at Low Field (1 T)
Aime, Silvio,Boutry, Sébastien,Granato, Luigi,Henoumont, Céline,Laurent, Sophie,Longo, Dario,Muller, Robert N.,Vander Elst, Luce
, (2019/11/14)
The synthesis of poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) dendrons Gd-based contrast agents (GdCAs) via an orthogonal protection of the different functional groups and an activation/coupling strategy wherein a specific number of synthetic steps add a generation to the existing dendron has been described. The aim of this protocol is to build up two different generations of dendrons (G-0 or dendron's core, and G-1) with peripheral NH2 groups to conjugate a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivative and afterwards to chelate with Gd3+ paramagnetic ions. These complexes, which have a well-defined molecular weight, are of relevance to MRI as an attempt to gain higher 1H relaxivity by slowing down the rotation of molecule compared to monomeric Gd(III) complexes used as contrast agents and to increase the number of paramagnetic centers present in one molecular structure. From the study of their water 1H longitudinal relaxation rate at different magnetic fields (NMRD, Nuclear Magnetic Relaxation Dispersion) and by evaluating the variable temperature 17O-NMR data we determined the parameters characterizing the water exchange rate and the rotational correlation time of each complex, both affecting 1H relaxivity. Furthermore, these two novel PAPGly GdCAs were objects of i) an in vivo study to determine their biodistributions in healthy C57 mice at several time points, and ii) the Dynamic Contrast-Enhanced MRI (DCE-MRI) approach to assess their contrast efficiency measured in the tumor region of C57BL/6 mice transplanted subcutaneously with B16-F10 melanoma cells. The aim of the comparison of these two dendrons GdCAs, having different molecular weights (MW), is to understand how MW and relaxivity may influence the contrast enhancement capabilities in vivo at low magnetic field (1 T). Significant contrast enhancement was observed in several organs (vessel, spleen and liver), already at 5 min post-injection, for the investigated CAs. Moreover, these CAs induced a marked contrast enhancement in the tumor region, thanks to the enhanced permeability retention effect of those macromolecular structures.
