Molecular imaging of matrix metalloproteinases in vivo using small molecule inhibitors for SPECT and PET.
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.
Wagner
S
S
Department of Nuclear Medicine, University Hospital Münster, Münster, Germany. stwagner@uni-muenster.de
Breyholz
H-J
HJ
Faust
A
A
Höltke
C
C
Levkau
B
B
Schober
O
O
Schäfers
M
M
Kopka
K
K
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000276:immunology; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases