Max Planck Institute for Biological Cybernetics, Department for Physiology of Cognitive Processes, Max-Planck-Ring 11, 72072 Tübingen, Germany.
Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, New York 10962, United States.
J Med Chem. 2021 Jun 10;64(11):7565-7574. doi: 10.1021/acs.jmedchem.1c00264. Epub 2021 May 7.
The relevance of MRI as a diagnostic methodology has been expanding significantly with the development of molecular imaging. Partially, the credit for this advancement is due to the increasing potential and performance of targeted MRI contrast agents, which are able to specifically bind distinct receptors or biomarkers. Consequently, these allow for the identification of tissues undergoing a disease, resulting in the over- or underexpression of the particular molecular targets. Here we report a multimeric molecular probe, which combines the established targeting properties of the Arg-Gly-Asp (RGD) peptide sequence toward the integrins with three calcium-responsive, Gd-based paramagnetic moieties. The bifunctional probe showed excellent H MRI contrast enhancement upon Ca coordination and demonstrated a longer retention time in the tissue due to the presence of the RGD moiety. The obtained results testify to the potential of combining bioresponsive contrast agents with targeting vectors to develop novel functional molecular imaging methods.
随着分子成像技术的发展，MRI 作为一种诊断方法的相关性显著扩大。部分原因是由于靶向 MRI 对比剂的潜力和性能不断提高，这些对比剂能够特异性地结合不同的受体或生物标志物。因此，这些对比剂可以识别发生疾病的组织，导致特定分子靶标过度或不足表达。在这里，我们报告了一种多聚分子探针，它将 Arg-Gly-Asp（RGD）肽序列对整合素的既定靶向特性与三个钙响应的 Gd 基顺磁部分结合在一起。双功能探针在 Ca 配位时表现出优异的 H MRI 对比增强效果，并由于存在 RGD 部分而在组织中表现出更长的保留时间。所得结果证明了将生物响应性对比剂与靶向载体结合以开发新型功能分子成像方法的潜力。
