**2. Radipharmaceuticals for molecular imaging of apoptosis**

After the initial description of apoptosis based on the morphological features, several useful biochemical and immunohistochemical detection methods were subsequently introduced based on the understanding of the basic mechanisms of apoptosis. As a histochemical technique for the detection of apoptosis, terminal deoxynucleotidyltransferase-dUTP-nick endlabeling (TUNEL) assays has become a standard technique for in situ labeling and localization of DNA breaks in individual nuclei on tissue section (Gavrieli, et al.,1992). TUNEL is based on the specific binding of terminal deoxynucleotidyltransferase (TdT) to 3'-OH ends of fragmented DNA. As DNA ladder formation is quite a late feature of apoptosis, TUNEL assay appears to be uniquely associated with apoptotic cell death. For the in-vivo imaging initiator caspases and effector caspases can be distinguished and serve as potential targets inside the apoptotic cells. However, for molecular target for in-vivo imaging, it is favorable that the target exists on cell surface rather than in cytoplasm or nucleus. Accordingly, to date, most noninvasive imagings of apoptosis target PS on the cell membrane, which is a membrane aminophospholipid that is normally located on the inner leaflet of cell membrane but is rapidly trnaslocated to the outer leaflet of cell membrane once the cell become apoptotic. Annexin V, a 36-kD physiologic protein, binds with nanomolar affinity to PS in a calcium dependent manner, therefore, 99mTc labeled annexin V permits imaging of apoptosis in vivo in its early stage (Blankenberg, et al., 1998; Hofstra, et al., 2000; Kemerink, et al., 2003).
