Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation

Verena Hugenberg*, Stefan Wagner, Klaus Kopka, Michael Schäfers, Robert C. Schuit, Albert D. Windhorst, Sven Hermann

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)307-321
Number of pages15
JournalJournal of Medicinal Chemistry
Volume60
Issue number1
DOIs
Publication statusPublished - 12 Jan 2017

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