Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925 Alcorcón, Madrid, Spain.
Molecules. 2019 Aug 16;24(16):2982. doi: 10.3390/molecules24162982.
Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases which are secreted or anchored in the cell membrane and are capable of degrading the multiple components of the extracellular matrix (ECM). MMPs are frequently overexpressed or highly activated in numerous human diseases. Owing to the important role of MMPs in human diseases, many MMP inhibitors (MMPIs) have been developed as novel therapeutics, and some of them have entered clinical trials. However, so far, only one MMPI (doxycycline) has been approved by the FDA. Therefore, the evaluation of the activity of a specific subset of MMPs in human diseases using clinically relevant imaging techniques would be a powerful tool for the early diagnosis and assessment of the efficacy of therapy. In recent years, numerous MMPIs labeled imaging agents have emerged. This article begins by providing an overview of the MMP subfamily and its structure and function. The latest advances in the design of subtype selective MMPIs and their biological evaluation are then summarized. Subsequently, the potential use of MMPI-labeled diagnostic agents in clinical imaging techniques are discussed, including positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging (OI). Finally, this article concludes with future perspectives and clinical utility.
基质金属蛋白酶（MMPs）是一类锌和钙离子依赖性内肽酶，它们分泌或锚定在细胞膜上，能够降解细胞外基质（ECM）的多种成分。MMPs 在许多人类疾病中经常过度表达或高度激活。由于 MMPs 在人类疾病中的重要作用，许多基质金属蛋白酶抑制剂（MMPI）已被开发为新型治疗药物，其中一些已进入临床试验。然而，迄今为止，只有一种 MMPIs（强力霉素）获得了 FDA 的批准。因此，使用临床相关的成像技术评估人类疾病中特定 MMPs 亚群的活性将是早期诊断和评估治疗效果的有力工具。近年来，出现了许多 MMPIs 标记的成像剂。本文首先概述了 MMP 亚家族及其结构和功能。然后总结了设计亚型选择性 MMPIs 及其生物学评价的最新进展。随后，讨论了 MMPIs 标记的诊断剂在临床成像技术中的潜在用途，包括正电子发射断层扫描（PET）、单光子发射计算机断层扫描（SPECT）和光学成像（OI）。最后，本文对未来的展望和临床应用进行了总结。
