Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes

Laura E. Edgington; Alicia B. Berger; Galia Blum; Victoria E. Albrow; Margot G. Paulick; Neil Lineberry; Matthew Bogyo

doi:10.1038/nm.1938

Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes

Laura E. Edgington, Alicia B. Berger, Galia Blum, Victoria E. Albrow, Margot G. Paulick, Neil Lineberry, Matthew Bogyo^*

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

244 Scopus citations

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.

Original language	American English
Pages (from-to)	967-973
Number of pages	7
Journal	Nature Medicine
Volume	15
Issue number	8
DOIs	https://doi.org/10.1038/nm.1938
State	Published - Aug 2009

Bibliographical note

Funding Information:
We would like to thank G. Salvesen from the Burnham Institute for Medical Research for the kind gift of recombinant caspases and for creative input on the project. We thank B. Sloane, Wayne State University, for the kind gift of cathepsin antibodies and C. Watts of the University of Dundee for the kind gift of legumain antibodies. We thank R. Weimer for critical discussion of the data and help with protocols for the use of Apomab. We thank A. Fan and D. Felsher for assistance with the MYC mouse model. We thank the Molecular Imaging Program at Stanford and the Stanford Small Animal Imaging Facility for assistance with noninvasive imaging studies. This work was funded by US National Institutes of Health grants U54 RR020843 and R01 EB005011 (to M.B.). M.G.P. was supported by Public Health Services grant CA09302, awarded by the US National Cancer Institute, Department of Health and Human Services.

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title = "Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes",

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.",

author = "Edgington, {Laura E.} and Berger, {Alicia B.} and Galia Blum and Albrow, {Victoria E.} and Paulick, {Margot G.} and Neil Lineberry and Matthew Bogyo",

note = "Funding Information: We would like to thank G. Salvesen from the Burnham Institute for Medical Research for the kind gift of recombinant caspases and for creative input on the project. We thank B. Sloane, Wayne State University, for the kind gift of cathepsin antibodies and C. Watts of the University of Dundee for the kind gift of legumain antibodies. We thank R. Weimer for critical discussion of the data and help with protocols for the use of Apomab. We thank A. Fan and D. Felsher for assistance with the MYC mouse model. We thank the Molecular Imaging Program at Stanford and the Stanford Small Animal Imaging Facility for assistance with noninvasive imaging studies. This work was funded by US National Institutes of Health grants U54 RR020843 and R01 EB005011 (to M.B.). M.G.P. was supported by Public Health Services grant CA09302, awarded by the US National Cancer Institute, Department of Health and Human Services.",

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AU - Lineberry, Neil

AU - Bogyo, Matthew

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Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes

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