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)

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) (77 views visite)

Granato L, Longo D, Boutry S, Vander Elst L, Henoumont C, Aime S, Muller RN, Laurent S

Chem Biodivers (ISSN: 1612-1872linking), 2019 Nov; 16(11): e1900322-e1900322.

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Paper type Tipo di articolo: Journal Article

Impact factor: 1.449, 5-year impact factor Impact factor a 5 anni: 0

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Keywords Parole chiave: Animals, Contrast Media Chemical Synthesis Chemistry Pharmacokinetics, Gadolinium Chemistry Pharmacokinetics, Humans, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Melanoma Chemistry Diagnostic Imaging, Inbred C57bl, Molecular Structure, Neoplasms, Experimental Chemistry Diagnostic Imaging, Organometallic Compounds Chemical Synthesis Chemistry Pharmacokinetics, Tissue Distribution, Dendrimers, Gadolinium Complexes, Mri

Affiliations Affiliazioni:
*** IBB - CNR ***

General, Organic and Biomedical Chemistry Unit, NMR and Molecular Imaging Laboratory, University of Mons, 19 avenue Maistriau, B-7000, Mons, Belgium.
Institute of Biostructures and Bioimaging (IBB), Italian National Research Council (CNR), I-10124, Torino, Italy.
Center for Microscopy and Molecular Imaging, 8 rue Adrienne Bolland, B-6041, Charleroi, Belgium.
Department of Molecular Biotechnology and Health Sciences, University of Torino, I-10124, Torino, Italy.

References Riferimenti:
Not available. Non disponibili.

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)

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 NH(2) groups to conjugate a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivative and afterwards to chelate with Gd(3+) paramagnetic ions. These complexes, which have a well-defined molecular weight, are of relevance to MRI as an attempt to gain higher (1) H 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 (1) H longitudinal relaxation rate at different magnetic fields (NMRD, Nuclear Magnetic Relaxation Dispersion) and by evaluating the variable temperature (17) O-NMR data we determined the parameters characterizing the water exchange rate and the rotational correlation time of each complex, both affecting (1) H 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.