Molecular imaging of proteolytic activity in cancer.
The early detection of both primary tumors and metastatic disease continue to be significant challenges in the diagnosis and staging of cancer. The growing recognition of the role of proteinases and proteolytic cascades in both the growth and metastasis of tumors has led to the development not only of therapeutic strategies using proteinase inhibitors, but also of methods to detect and image tumors in vivo via tumor-associated proteolytic activities. These imaging strategies derive from the enhanced sensitivity afforded by amplification that can be obtained by enzymatic processing to increase the efficacy of imaging "contrast agents" coupled with the inherent substrate specificity and selectivity of proteinases. This review describes key proteinases important in cancer progression, the strategies that have been devised to detect and image proteolytic activity in vivo, and the potential for this kind of functional imaging to serve as a marker for targeted therapy. The intent is to draw attention to the developing methods of molecular imaging to facilitate not only cancer diagnosis, but also for devising strategies for individualized targeted therapy and non-invasive monitoring of therapeutic efficacy.
McIntyre
J Oliver
JO
Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232-6840, USA. oliver.mcintyre@vanderbilt.edu
Matrisian
Lynn M
LM
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D003952:Diagnostic Imaging; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D010450:Endopeptidases; D020783:Matrix Metalloproteinase 7