Imaging cell death in vivo.

A technique to image programmed cell death would be useful both in clinical care and in drug development. The most widely studied agent for the in vivo study of apoptosis is radiolabeled annexin V, an endogenous protein labeled with technectium-99m, now undergoing clinical trials in both Europe and the United States. While annexin V has been studied extensively in humans the precise mechanism(s) of uptake this agent in vivo is unclear and needs further study. Other agents are also under development, including radiolabeled forms of Z-VAD.fmk, a potent inhibitor of the enzymatic cascade intimately associated with apoptosis. In addition other technologies, such as diffusion weighted magnetic resonance imaging and magnetic resonance imaging with contrast agents, such as small paramagnetic iron oxide particles coated with peptides have also been advocated as methods to monitor apoptotic cell death. The potential applications of imaging apoptosis as a marker of early response to therapy in cancer, acute cerebral and myocardial ischemic injury and infarction, immune mediated inflammatory disease and transplant rejection are reviewed.