Dipartimento di Scienze dell'Ambiente e della Vita, Università degli Studi del Piemonte Orientale Amedeo Avogadro, Viale T. Michel 11, 15121 Alessandria, Italy.
Bioorg Med Chem. 2011 Feb 1;19(3):1115-22. doi: 10.1016/j.bmc.2010.07.064. Epub 2010 Aug 2.
The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L(1), L(2) and L(3)) were designed as modified acyclic polyaminocarboxylate chelates by introducing an l-tyrosine residue in place of an aminoacetate unit. The corresponding Mn(II) complexes were fully characterised by (1)H NMR relaxometric techniques in aqueous media. The responsive activity towards the expression of tyrosinase was then assessed by monitoring the (1)H 1/T(1) relaxivity changes during incubation experiments in buffered solutions containing tyrosinase at different concentrations and in B16F10 melanoma cell homogenate. New insight on the mechanism of action of these systems was gained by measuring the magnetic field dependence of the relaxivity and ESR spectra of the incubated solutions. The systems developed showed responsive activity to tyrosinase with a relaxation enhancement spanning from 50% (MnL(1)) to 350% (MnL(3)) which augurs well for the development of diagnostic probes to detect melanoma cancer.
本文描述了一种新型 Mn(II)基 MRI/分子成像探针的研究，该探针可响应酶酪氨酸，用于潜在的诊断应用。酶酪氨酸是一种氧化还原酶，在黑色素瘤癌细胞中表达上调。通过在无环聚氨羧酸盐螯合物中引入 l-酪氨酸残基代替氨基乙酸单元，设计了三个新型配体（L(1)、L(2)和 L(3)）。通过（1）H NMR 弛豫技术在水介质中对相应的 Mn(II)配合物进行了全面表征。然后通过在含有不同浓度酪氨酸酶的缓冲溶液中和 B16F10 黑色素瘤细胞匀浆中进行孵育实验，监测（1）H 1/T(1)弛豫率的变化，评估它们对酪氨酸酶表达的响应活性。通过测量孵育溶液的弛豫率和 ESR 谱的磁场依赖性，获得了这些体系作用机制的新见解。所开发的系统对酪氨酸酶具有响应活性，弛豫增强幅度从 50%（MnL(1)）到 350%（MnL(3)），这为开发用于检测黑色素瘤癌症的诊断探针提供了良好的前景。
