Development of a Dendritic Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) Contrast Agent: Synthesis, Toxicity (in Vitro) and Relaxivity (in Vitro, in Vivo) Studies

Abstract

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.