Apoptosis is an important mechanism in cellular homeostasis and imbalances in the apoptotic process are associated with various disease states. An important example is the acquired ability of cancer cells to resist their own programmed cell death and therefore it is the aim of many tumor therapies to either reestablish pro-apoptotic signaling pathways or induce apoptosis through activation of existing mechanisms within the cell. Therefore, visualizing and quantifying the apoptotic process in vivo has great value in monitoring therapy response, diagnosis and staging disease.
By being able to detect subtle changes in perfusion and tissue oxygenation, the small animal Multispectral Optoacoustic Tomography (MSOT) scanner offers unprecedented performance in cross-sectional imaging of tumor heterogeneity as well as a powerful capacity to simultaneously image molecular processes such as apoptosis by utilizing novel molecular probes. In this study, apoptotic regions within a mouse mammary tumor where visualized using a dye-conjugated caspase probe and compared to the hypoxia status of each tumor region.
The temporal resolution of the MSOT small animal scanner (generation of multispectral cross-sectional data in less than 1 second) allows for the dynamic imaging of targeted and control probe simultaneously. To illustrate this point apoptosis probe was co-injected with a control dye with similar physical and chemical properties, but a different absorbance maximum after which the tumor region was imaged over 1 hour with multi-spectral image acquisition. Next, mice were imaged by MSOT immediately before and 24 hours post treatment with the chemotherapeutic Doxorubicin and the induction of apoptosis was visualized and quantified. Doxorubicin treatment led to a significant increase in signal resulting from the DyLight 747-conjugated apoptosis probe. In summary, MSOT can be used to determine the extent of apoptosis in tumors in vivo and thus has great value in monitoring therapy response, diagnosis and staging disease.
Citation Format: Wouter H. Driessen, Neal C. Burton, Thomas Sardella, Stefan Morscher, Daniel Razansky, Vasilis Ntziachristos. Multispectral Optoacoustic Tomography (MSOT) imaging and quantification of apoptosis in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 737. doi:10.1158/1538-7445.AM2013-737