Abstract
Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases. MMPs are involved in many physiological processes but also take part in the pathophysiological mechanisms responsible for a wide range of diseases. Pathological expression and activation of MMPs are associated with cancer, atherosclerosis, stroke, arthritis, periodontal disease, multiple sclerosis and liver fibrosis. Thus, noninvasive visualisation and quantification of MMP activity in vivo are of great interest in basic research and clinical application. This can be achieved by scintigraphic molecular imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provided suitable radiolabelled tracers exist, e.g. radioactive inhibitors of matrix metalloproteinases (MMPIs). The approach to monitor MMP activity in vivo using radiolabelled small molecule inhibitors suitable for SPECT and PET is summarised in this review. Briefly, latest advances in scintigraphic imaging are introduced and followed by a report about the enzyme class of MMPs. The involvement of MMPs in cancer and atherosclerosis is exemplified and small molecule MMPIs are classified. Subsequently, the development of radiolabelled small molecule MMPIs, their synthesis and in vitro and in vivo evaluation is reviewed. Finally, an outlook on the clinical potential of labelled MMPIs in diagnostic algorithms is given.
Keywords: Matrix metalloproteinases, radiolabelled inhibitors of matrix metalloproteinases, CGS 27023A, molecular imaging, positron emission tomography PET, single photon emission computed tomography SPECT
Current Medicinal Chemistry
Title: Molecular Imaging of Matrix Metalloproteinases In Vivo Using Small Molecule Inhibitors for SPECT and PET
Volume: 13 Issue: 23
Author(s): S. Wagner, H.-J. Breyholz, A. Faust, C. Holtke, B. Levkau, O. Schober, M. Schafers and K. Kopka
Affiliation:
Keywords: Matrix metalloproteinases, radiolabelled inhibitors of matrix metalloproteinases, CGS 27023A, molecular imaging, positron emission tomography PET, single photon emission computed tomography SPECT
Abstract: Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases. MMPs are involved in many physiological processes but also take part in the pathophysiological mechanisms responsible for a wide range of diseases. Pathological expression and activation of MMPs are associated with cancer, atherosclerosis, stroke, arthritis, periodontal disease, multiple sclerosis and liver fibrosis. Thus, noninvasive visualisation and quantification of MMP activity in vivo are of great interest in basic research and clinical application. This can be achieved by scintigraphic molecular imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provided suitable radiolabelled tracers exist, e.g. radioactive inhibitors of matrix metalloproteinases (MMPIs). The approach to monitor MMP activity in vivo using radiolabelled small molecule inhibitors suitable for SPECT and PET is summarised in this review. Briefly, latest advances in scintigraphic imaging are introduced and followed by a report about the enzyme class of MMPs. The involvement of MMPs in cancer and atherosclerosis is exemplified and small molecule MMPIs are classified. Subsequently, the development of radiolabelled small molecule MMPIs, their synthesis and in vitro and in vivo evaluation is reviewed. Finally, an outlook on the clinical potential of labelled MMPIs in diagnostic algorithms is given.
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Wagner S., Breyholz H.-J., Faust A., Holtke C., Levkau B., Schober O., Schafers M. and Kopka K., Molecular Imaging of Matrix Metalloproteinases In Vivo Using Small Molecule Inhibitors for SPECT and PET, Current Medicinal Chemistry 2006; 13 (23) . https://dx.doi.org/10.2174/092986706778522002
DOI https://dx.doi.org/10.2174/092986706778522002 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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