Journal article Open Access

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

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

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.

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