title: In vitro and ex vivo evaluation of smart infra-red fluorescent caspase-3 probes for molecular imaging of cardiovascular apoptosis.
abstract: Purpose. The aim of this paper is to develop new optical bioprobes for the imaging of apoptosis. Procedure. We developed quenched near-infrared probes which become fluorescent upon cleavage by caspase-3, the key regulatory enzyme of apoptosis. Results. Probes were shown to be selectively cleaved by recombinant caspase-3. Apoptosis of cultured endothelial cells was associated with an increased fluorescent signal for the cleaved probes, which colocalized with caspase-3 and was reduced by the addition of a caspase-3 inhibitor. Flow cytometry demonstrated a similar profile between the cleaved probes and annexin V. Ex vivo experiments showed that sections of hearts obtained from mice treated with the proapoptotic drug doxorubicin displayed an increase in the fluorescent signal for the cleaved probes, which was reduced by a caspase-3 inhibitor. Conclusion. We demonstrated the capacity of these novel probes to detect apoptosis by optical imaging in vitro and ex vivo.
authors.affiliation: Inserm U644 and Rouen University Hospital, Institute for Biomedical Research and IRFMP23, University of Rouen, 76183 Rouen, France.
authors.forename: Manuelle
authors.initials: M
authors.lastname: Debunne
authors.forename: Christophe
authors.initials: C
authors.lastname: Portal
authors.forename: Bruno
authors.initials: B
authors.lastname: Delest
authors.forename: Ebba
authors.initials: E
authors.lastname: Brakenhielm
authors.forename: Françoise
authors.initials: F
authors.lastname: Lallemand
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Henry
authors.forename: Heidi
authors.initials: H
authors.lastname: Ligeret
authors.forename: Pauline
authors.initials: P
authors.lastname: Noack
authors.forename: Marc
authors.initials: M
authors.lastname: Massonneau
authors.forename: Anthony
authors.initials: A
authors.lastname: Romieu
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Renard
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard