Radiotracers for noninvasive molecular imaging of tumor cell death

The need to monitor cancer therapy-induced cellular and tissue changes using noninvasive imaging techniques continues to stimulate both basic and clinical research. Monitoring changes in cellular proliferative capacity that occur after treatment with radiation and/or chemotherapy has the potential to provide longitudinal information on the cellular dynamics of tumors before, during, and after therapeutic intervention. Cells can lose their reproductive potential through one of several mechanisms, including apoptosis and autophagy (which are forms of programmed cell death), premature senescence, or necrosis. When a tumor responds to therapy, current imaging methods do not provide information about the exact mechanism of cell death executed. We are now beginning to develop the molecular imaging tools that will enable us to noninvasively image cell death mechanisms both in experimental models and in the clinical cancer environment. Studies with these imaging tools will contribute to a better understanding of therapeutic responses and assist in the design and evaluation of more effective treatments. This review examines the state-of-the-art in the use of (radio)tracers for the purpose of imaging mechanisms of tumor cell inactivation (cell death) in animal models and in clinical trials.