Will imaging of apoptosis play a role in clinical care? A tale of mice andmen

Programmed cell death (apoptosis) plays a role in the pathophysiology of ma ny diseases and in the outcome of treatment. Apoptosis is the likely mechan ism behind the cytoreductive effects of standard chemotherapeutic and radia tion treatments, rejection of organ transplants, cellular damage in collage n vascular disorders, and delayed cell death due to hypoxic-ischemic injury in myocardial infarction and neonatal hypoxic ischemic injury. Observation s about the role of apoptosis have fueled the development of novel agents a nd treatment strategies specifically aimed at inducing or inhibiting apopto sis. Despite these research developments there are no clinical entities where sp ecific measures of apoptosis are used in either diagnosis or patient manage ment. Part of the difficulty in bridging the gap between the basic science understanding of apoptosis and the clinical application of this information is the lack of a sensitive marker to monitor programmed cell death in asso ciation with disease progression or regression. Technetium-99m labeled anne xin V localizes at sites of apoptosis in-vivo, due to its nanomolar affinit y for membrane bound phosphatidylserine. Radiolabeled annexin V imaging per mits identification of the site and extent of apoptosis in experimental ani mals. Annexin V has been successfully used in animal models to image organ transplant rejection, characterize successful therapy of tumors, pinpoint a cute myocardial infarction, and identify hypoxic ischemic brain injury of t he newborn and adult. Early studies in human subjects suggest that Tc-99m a nnexin imaging will be also be useful to identify rejection in transplant r ecipients, localize acute myocardial infarction, and characterize the effec tiveness of a single treatment in patients with tumors. This review describes the imaging approaches to detect and monitor apoptosi s in-vivo that are presently in early clinical trials. The preliminary data are extrapolated to identify conditions where apoptosis imaging may be val uable in clinical decision making. These conditions include: transplant rej ection; hypoxic/ischemic injury of heart and brain; and determining the eff icacy of therapy in cancer, heart failure and osteoporosis.