title: Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation.
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.
authors.affiliation: European Institute for Molecular Imaging, University of Münster , Waldeyerstrasse 15, D-48149 Münster, Germany.|Department of Nuclear Medicine, University Hospital Münster , Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany.
authors.forename: Verena
authors.identifier: 0000-0001-5677-6674
authors.initials: V
authors.lastname: Hugenberg
authors.affiliation: Department of Nuclear Medicine, University Hospital Münster , Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Department of Nuclear Medicine, University Hospital Münster , Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kopka
authors.affiliation: European Institute for Molecular Imaging, University of Münster , Waldeyerstrasse 15, D-48149 Münster, Germany.|Department of Nuclear Medicine, University Hospital Münster , Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany.|DFG EXC 1003 Cluster of Excellence "Cells in Motion", University of Münster , D-48149 Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center Amsterdam , De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schuit
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center Amsterdam , De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: European Institute for Molecular Imaging, University of Münster , Waldeyerstrasse 15, D-48149 Münster, Germany.|DFG EXC 1003 Cluster of Excellence "Cells in Motion", University of Münster , D-48149 Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; D019275:Radiopharmaceuticals; D053509:Matrix Metalloproteinase 13