title: PET imaging of in vivo caspase-3/7 activity following myocardial ischemia-reperfusion injury with the radiolabeled isatin sulfonamide analogue [(18)F]WC-4-116.
abstract: The utility of [(18)F]WC-4-116, a PET tracer for imaging caspase-3 activation, was evaluated in an animal model of myocardial apoptosis. [(18)F]WC-4-116 was injected into rats at 3 hours after a 30 min period of ischemia induced by temporary occlusion of the left anterior descending coronary artery in Sprague-Dawley rats. [(18)F]WC-4-116 uptake was quantified by 1) autoradiography, 2) microPET imaging studies, and 3) post-PET biodistribution studies. MicroPET imaging also assessed uptake of the non-caspase-3-targeted tracer [(18)F]ICMT-18 at 3 hours postischemia. Enzyme assays and Western blotting assessed caspase-3 activation in both at-risk and not-at-risk regions. Caspase-3 enzyme activity increased in the at-risk but not in the not-at-risk myocardium. Quantitative autoradiographic analysis of [(18)F]WC-4-116 demonstrated nearly 2-fold higher uptake in the ischemia-reperfusion (IR) versus sham animals. [(18)F]WC-4-116 microPET imaging studies demonstrated that the IR animals was similarly elevated in relation to sham. [(18)F]ICMT-18 uptake did not increase in at-risk myocardium despite evidence of caspase-3 activation. Biodistribution studies with [(18)F]WC-4-116 confirmed the microPET findings. These data indicate that the caspase-3-PET tracer [(18)F]WC-4-116 can noninvasively image in vivo caspase activity during myocardial apoptosis and may be useful for clinical imaging in humans.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of MedicineSt. Louis, MO 63110, USA; Cardiovascular Division, Washington University School of MedicineSt Louis, MO 63110, USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Thukkani
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of MedicineSt. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University School of MedicineSt. Louis, MO 63110, USA.
authors.forename: Kooresh I
authors.initials: KI
authors.lastname: Shoghi
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine St. Louis, MO 63110, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine St. Louis, MO 63110, USA.
authors.forename: Jinbin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine St. Louis, MO 63110, USA.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Chu
authors.affiliation: Cardiovascular Division, Washington University School of Medicine St Louis, MO 63110, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Novak
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine St. Louis, MO 63110, USA.
authors.forename: Delphine L
authors.initials: DL
authors.lastname: Chen
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of MedicineSt. Louis, MO 63110, USA; Cardiovascular Division, Washington University School of MedicineSt Louis, MO 63110, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gropler
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of MedicineSt. Louis, MO 63110, USA; Department of Cell Biology & Physiology, Washington University School of MedicineSt. Louis, MO 63110, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of MedicineSt. Louis, MO 63110, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
keywords: Isatin sulfonamide analogue; PET; apoptosis; caspase; tracer