Department Science and Technological Innovation, University of Piemonte Orientale, Viale Teresa Michel 11, 15121, Alessandria, Italy.
Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza, 52, 10126, Torino, Italy.
ChemMedChem. 2022 Dec 16;17(24):e202200508. doi: 10.1002/cmdc.202200508. Epub 2022 Oct 27.
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 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 s of the Mn(II)-complex to 14.0 mM s 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.
一种基于 1,4-DO2A（DO2A=四氮杂环十二烷-1,4-二乙酸）的双酰胺衍生物的稳定惰性两亲性 Mn(II)配合物被合成，并研究了其 H NMR 弛豫性能作为磁场强度、pH 值和温度的函数。通过弛豫率研究了与人血清白蛋白（HSA）的相互作用，结果表明在低场下具有很好的弛豫增强效果（在 1T 和 298 K 时，Mn(II)-配合物的弛豫率从 4.5 mM s 增加到配合物-HSA 超分子加合物的 14.0 mM s）。体内分布和 MRI 研究表明，从健康小鼠中快速混合的肾脏/肝脏清除，没有脾脏积累，并且在乳腺肿瘤小鼠模型中具有良好的对比增强特性。与临床批准的 Gd(III)试剂（GdBOPTA，Multihance®）的比较表明，所提出的 Mn(II)造影剂在注射后 3 小时内可提供可比的肿瘤对比增强效果。
