Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation.
Creators
- 1. European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany and Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany
- 2. Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany
- 3. European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany and DFG EXC 1003 Cluster of Excellence 'Cells in Motion', University of Münster, D-48149 Münster, Germany
- 4. Department of Radiology & Nuclear Medicine, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands
- 5. European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany and DFG EXC 1003 Cluster of Excellence 'Cells in Motion', University of Münster, D-48149 Münster, Germany
Description
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.
Files
Hugenberg_JMedChem_2017-P01-AAM.pdf
Files
(2.0 MB)
| Name | Size | Download all |
|---|---|---|
|
md5:6a97ceea5235860f98980996dca53ea3
|
2.0 MB | Preview Download |