Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes.
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.
Edgington
Laura E
LE
Cancer Biology Program, Stanford University School of Medicine, Stanford, California, USA.
Berger
Alicia B
AB
Blum
Galia
G
Albrow
Victoria E
VE
Paulick
Margot G
MG
Lineberry
Neil
N
Bogyo
Matthew
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D003907:Dexamethasone / Q000627:therapeutic use; D003952:Diagnostic Imaging / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods; D004789:Enzyme Activation / Q000502:physiology; D005456:Fluorescent Dyes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D055620:Optical Phenomena; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D005456:Fluorescent Dyes; D003907:Dexamethasone; D020169:Caspases