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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

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    <dct:description>&lt;p&gt;The noninvasive imaging of MMP activity in vivo could have a&lt;br&gt; high impact in basic research as well as in clinical applications. This approach&lt;br&gt; can be established using radiolabeled MMP inhibitors (MMPIs) as tracers for&lt;br&gt; the detection of activated MMPs by means of PET. However, the complexity of&lt;br&gt; diseases associated with dysregulated MMP expression necessitates the imaging&lt;br&gt; of distinct MMPs or MMP subgroups to distinguish their individual role in&lt;br&gt; specific diseases. To this end, selective and potent MMP-13 inhibitors based on&lt;br&gt; a N,N′-bis(benzyl)pyrimidine-4,6-dicarboxamide core have been synthesized&lt;br&gt; and successfully radiolabeled with carbon-11, fluorine-18, and gallium-68.&lt;br&gt; Selected radiolabeled candidates were evaluated in vitro and in vivo regarding&lt;br&gt; their pharmacokinetic properties and metabolic stability.&lt;/p&gt;</dct:description>
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Publication date:
January 12, 2017
DOI:
10.1021/acs.jmedchem.6b01284
Keyword(s):
Selective matrix metalloproteinase inhibitors selective MMP-13 inhibitors positron emission tomography radiotracer
Published in:
J. Med. Chem.: 60 pp. 307–321 (1).
Grants:
European Commission:
Communities:
License (for files):
Creative Commons Attribution 4.0 International

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