Imaging of apoptosis.

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.