Nuclear imaging of apoptosis in animal tumor models

Apoptosis or programmed cell death is a highly regulated multistep process leading to selective cell death and elimination without a concomitant inflammatory reaction of surrounding tissue. A number of physiological processes including tissue renewal, wound healing, and elimination of activated immune cells, when they have accomplished their function, depend on intact apoptosis. Apoptosis may also be triggered by several external stimuli including drugs, toxins, gamma irradiation, growth factors withdrawal and stimulation with cytokines of TNF family. Here, we focus our attention on drug-induced apoptosis in tumors. Most anticancer agents can induce a series of different cellular responses which ultimately result in the activation of common apoptotic pathways. Tumors that are unable to activate the apoptotic machinery in response to a death signal are therefore potentially resistant to treatment. Conversely, the early increase of the number of apoptotic cells after initial administration of drugs may be predictive of a favourable final outcome of treatment. Recently, non-invasive in vivo detection of activated apoptotic pathways has been proven to be suitable both in pre-clinical and clinical settings using nuclear medicine techniques. A number of radioligands mainly based on annexin V molecule have been developed and tested in animal models. Although some of them have been transferred to clinical studies, no definitive guidelines for apoptosis imaging are available at present. Nevertheless, many important clues may be derived by previous imaging studies and serve as a guidance. In this chapter we will primarily focus on critical issues that need to be addressed in the design and execution of imaging studies for non-invasive detection of apoptosis in animal tumor models.