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A Neutral and Stable Macrocyclic Mn(II) Complex for MRI Tumor Visualization

A stable and inert amphiphilic Mn(II) complex based on a bisamide derivative of 1,4‐DO2A (DO2A=tetraazacyclododecane‐1,4‐diacetic acid) was synthesized and its 1H NMR relaxometric behavior was investigated as a function of the magnetic field strength, pH and temperature. The interaction with human serum albumin (HSA) was also studied via relaxometry showing a good relaxivity enhancement at low field (at 1T and 298 K the relaxivity increases from 4.5 mM−1 s−1 of the Mn(II)‐complex to 14.0 mM−1 s−1 of the complex‐HSA supramolecular adduct). In vivo biodistribution and MRI studies highlighted a rapid and mixed renal/liver elimination without spleen accumulation from healthy mice and good contrast enhancing properties in a breast tumor murine model. A comparison with a clinically approved Gd(III) agent (GdBOPTA, Multihance®) underlined that the proposed Mn(II) contrast agent gave comparable tumor contrast enhancement up to 3 hours post‐injection.