A Neutral and Stable Macrocyclic Mn(II) Complex for MRI Tumor Visualization. (27th October 2022)

• Record Type: Journal Article
• Authors: Leone, Loredana; Anemone, Annasofia; Carella, Antonella; Botto, Elena; Longo, Dario Livio; Tei, Lorenzo
• Is Part Of: ChemMedChem. Volume 17:Number 24(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-27
• Subjects: MRI -- contrast agent -- Manganese -- relaxometry -- tumor; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202200508
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: 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 1 H 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. Abstract : Research on contrast agents for magnetic resonance imaging has recently guided efforts toward paramagnetic Mn(II) and Fe(III) complexes as alternatives to the well‐established Gd(III)‐based agents regularly used in clinical settings.The new neutral Mn(II) complex MnDO2AMGly reported herein shows good relaxometric performance, no toxicity, and in vivo breast tumor contrast enhancement similar to that of GdBOPTA.