Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation
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- 作者：Verena HugenbergStefan Wagner ; Klaus Kopka ; Michael Schäfers ; Robert C. Schuit ; Albert D. Windhorst ; Sven Hermann
- 刊名：Journal of Medicinal Chemistry
- 出版年：2017
- 出版时间：January 12, 2017
- 年：2017
- 卷：60
- 期：1
- 页码：307-321
- 全文大小：790K
- ISSN：1520-4804
文摘
The noninvasive imaging of MMP activity in vivo could have a high impact in basic research as well as in clinical applications. This approach can be established using radiolabeled MMP inhibitors (MMPIs) as tracers for the detection of activated MMPs by means of PET. However, the complexity of diseases associated with dysregulated MMP expression necessitates the imaging of distinct MMPs or MMP subgroups to distinguish their individual role in specific diseases. To this end, selective and potent MMP-13 inhibitors based on a N,N′-bis(benzyl)pyrimidine-4,6-dicarboxamide core have been synthesized and successfully radiolabeled with carbon-11, fluorine-18, and gallium-68. Selected radiolabeled candidates were evaluated in vitro and in vivo regarding their pharmacokinetic properties and metabolic stability.