Development of a Dendritic Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) Contrast Agent: Synthesis, Toxicity (in Vitro) and Relaxivity (in Vitro, in Vivo) Studies
| Autor: | Jérôme Steibel, Anne-Isabelle Michou-Gallani, Jean-Louis Gallani, Annabelle Bertin, Delphine Felder-Flesch |
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| Rok vydání: | 2009 |
| Předmět: |
Dendrimers
Gadolinium Biomedical Engineering Contrast Media Pharmaceutical Science chemistry.chemical_element Bioengineering Manganese Sensitivity and Specificity Magnetics Nuclear magnetic resonance In vivo medicine Animals Tissue Distribution Chelation Pharmacology medicine.diagnostic_test Chemistry Organic Chemistry Magnetic resonance imaging Pentetic Acid Magnetic Resonance Imaging Controlled release In vitro Rats Molecular Weight Solubility Toxicity Hydrophobic and Hydrophilic Interactions Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 20:760-767 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc8004683 |
| Popis: | A new dendritic manganese(II) chelate 1 has been evaluated by in vivo (relaxivity) and in vitro (toxicity and relaxivity) experiments as a manganese enhanced magnetic resonance imaging (MEMRI) contrast agent. Also, a comparison with its corresponding gadolinium(III) homologue 2 and the commercially available MEMRI agent MnDPDP (Teslascan, Amersham Health) was achieved in order to determine respectively the real influence of the paramagnetic ion in terms of toxicity and relaxivity for this precise treelike structure and the potential of 1 to be a favorable candidate for brain-targeting MRI. Complexes 1 and 2 displayed high hydrosolubility (0.1 M) and revealed no in vitro neuronal toxicity at concentrations as high as 1 mM. Considering manganese(II) complex 1, the in vivo nontoxicity at 20 mM (100% rats survival) is very likely due to a slow diffusion of the compound, meaning a controlled release of the paramagnetic ions. Finally, T(1) relaxivity of 4.2 mM(-1).s(-1) for 2 and T(2) relaxivity of 17.4 mM(-1).s(-1) for 1 at 4.7 T were measured and are higher than that of the commercial MRI contrast agents GdDTPA and MnDPDP, respectively. |
| Databáze: | OpenAIRE |
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