Technical Report abstract
Nature Medicine 15, 967 - 973 (2009)
Published online: 13 July 2009 | doi:10.1038/nm.1938
Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes
Laura E Edgington1,6, Alicia B Berger1,6, Galia Blum2,5,6, Victoria E Albrow2, Margot G Paulick2, Neil Lineberry3 & Matthew Bogyo1,2,4
Abstract
Imaging agents that enable direct visualization and quantification of apoptosis in vivo have great potential value for monitoring chemotherapeutic response as well as for early diagnosis and disease monitoring. We describe here the development of fluorescently labeled activity-based probes (ABPs) that covalently label active caspases in vivo. We used these probes to monitor apoptosis in the thymi of mice treated with dexamethasone as well as in tumor-bearing mice treated with the apoptosis-inducing monoclonal antibody Apomab (Genentech). Caspase ABPs provided direct readouts of the kinetics of apoptosis in live mice, whole organs and tissue extracts. The probes produced a maximum fluorescent signal that could be monitored noninvasively and that coincided with the peak in caspase activity, as measured by gel analysis. Overall, these studies demonstrate that caspase-specific ABPs have the potential to be used for noninvasive imaging of apoptosis in both preclinical and clinical settings.
- Cancer Biology Program, Stanford University School of Medicine, Stanford, California, USA.
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
- Department of Immunology, Stanford University School of Medicine, Stanford, California, USA.
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
- Present address: School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
- These authors contributed equally to this work.
Correspondence to: Matthew Bogyo1,2,4 e-mail: mbogyo@stanford.edu
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