Theranostics 2012; 2(2):207-214. doi:10.7150/thno.3806

Short Research Communication

In Vivo Monitoring of Liver Damage Using Caspase-3 Probe

Michitaka Ozaki1, Sanae Haga1,2, Takeaki Ozawa3 ✉

1. Department of Molecular Surgery, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan;
2. The Japan Society for the Promotion of Science (JSPS), Tokyo, Japan;
3. Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Ozaki M, Haga S, Ozawa T. In Vivo Monitoring of Liver Damage Using Caspase-3 Probe. Theranostics 2012; 2(2):207-214. doi:10.7150/thno.3806. Available from

File import instruction


Real-time monitoring of cellular and organ conditions improves our understanding of various physiopathological phenomena. Such monitoring is expected to provide important alternatives for clinical diagnosis and therapy. We have sought to show physiopathological changes of organs as well as cells. Here, we present an example of in vivo imaging of liver states using the luciferase-based caspase-3 optical probe. We examined dynamic changes of apoptosis (caspase-3 activity) of a mouse liver as well as those of liver cells, proving that the emitted signals reflected the biochemically evaluated apoptotic cell death. In live liver cell (AML 12) experiments, the optical probe for caspase-3 activity emitted signals in response to Fas-ligand, staurosporine and hypoxia/reoxygenation, demonstrating that the probe can measure cellular apoptosis quantitatively. We therefore applied this probe for mouse liver ischemia/reperfusion (I/R) and drug-toxicity to liver. By expressing the probe in a mouse liver adenovirally, we imaged liver caspase-3 activity (i.e. apoptotic damage) non-invasively and chronologically in the hepatic I/R model of mice. The duration of liver ischemia affected the post-ischemic caspase-dependent damage. Ischemia (up to 60 min) enhanced liver damage after reperfusion, but prolonged ischemia (90 min of ischemia) induced not apoptotic cell death but necrotic cell death. Direct observations of the changes of organ conditions elucidated the dynamism of organ function and damage. These technologies clearly possess clinical relevance. They are expected to provide a new diagnostic tool for various clinical settings in the future.

Keywords: imaging, non-invasive monitoring, optical probe, bioluminescence, luciferase.