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Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis
Published on: February 16, 2015
Imaging of apoptosis
1Department of Laboratory Medicine, University of Washington, Seattle, WA 98195-7110, USA. tait@u.washington.edu
Abstract:
Cells can die by several pathways, such as accidental death, apoptosis, autophagy, pyroptosis, and oncosis. These are important in normal physiology and many disease states, such as cancer and cardiovascular disease. Specific biochemical changes occur in cells undergoing apoptosis that provide potential targets for molecular imaging agents. Several of these molecular steps have been evaluated to date, including phosphatidylserine exposure at the extracellular face of the plasma membrane, detected by proteins such as annexin V; caspase activation in the intracellular compartment, detected by labeled enzyme substrates or inhibitors; and mitochondrial membrane potential collapse, detected by reduced levels of phosphonium cations that normally accumulate in healthy mitochondria. Phase I clinical trials have been performed with 1 of these agents, annexin V. Future work will likely include development of new agents that detect targets not exploited by current agents, translational research on the significance of imaging the different forms of cell death, and further improvements in the techniques for labeling existing agents to improve sensitivity and reduce nonspecific background.
Insights
Researchers are developing molecular imaging agents to detect specific biochemical changes during apoptosis, a key cell death pathway relevant to diseases like cancer. Early clinical trials show promise for agents targeting phosphatidylserine exposure.
Area of Science:
- Biomedical imaging
- Cell biology
- Molecular diagnostics
Background:
- Cell death occurs through various pathways, including apoptosis, which is crucial in both normal physiology and diseases like cancer and cardiovascular disease.
- Apoptosis involves specific biochemical alterations that present potential targets for molecular imaging agents.
- Understanding and imaging cell death mechanisms are vital for disease diagnosis and monitoring.
Purpose of the Study:
- To review current molecular imaging strategies targeting apoptotic cells.
- To discuss the biochemical markers of apoptosis suitable for imaging.
- To highlight the potential of molecular imaging in understanding cell death in disease.
Main Methods:
- Evaluation of molecular imaging agents targeting phosphatidylserine exposure (e.g., annexin V).
- Detection of intracellular caspase activation using labeled substrates or inhibitors.
- Assessment of mitochondrial membrane potential collapse via phosphonium cation accumulation.
Main Results:
- Several molecular targets for apoptosis imaging have been identified and evaluated.
- Annexin V, targeting phosphatidylserine exposure, has undergone Phase I clinical trials.
- Current methods demonstrate feasibility but require further refinement for sensitivity and specificity.
Conclusions:
- Molecular imaging agents targeting apoptosis show significant potential for clinical applications.
- Future research should focus on novel imaging targets and improved labeling techniques.
- Translational studies are needed to elucidate the clinical significance of imaging diverse cell death forms.
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