Tc-Ethylenedicysteine-endostatin

Angiogenesis is the formation of new blood capillaries and vessels from existing vessels (1-3). It involves the degradation of the basal membrane surrounding the parental vasculature, and the proliferation of endothelial and smooth muscle cells to form new vessels, resulting in an improvement in tissue perfusion and function. The major stimuli for angiogenesis include ischemia, hypoxia, inflammation, and shear stress (4). A large number of endogenous angiogenic factors are involved in angiogenesis (5), including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-8 (IL-8), and transforming growth factor-β (TGF-β). Extracellular matrix and proteolytic enzymes as well as integrins are also involved during angiogenesis (6). There are also endogenous inhibitors of angiogenesis such as, angiostatin, endostatin and platelet factor-4 (7, 8). Tumor angiogenesis represents a continuous and important process in tumor development in which the tumor attempts to gain an independent blood supply (9). This process is driven by the tumor's chronic overproduction of angiogenic factors, which bind to receptors on nearby vessel endothelial cells. Angiogenesis is essential for the growth of solid tumors and their metastases. Imaging angiogenesis may be useful for monitoring angiogenic treatments of tumors and cardiovascular diseases (3, 10, 11). Endostatin was discovered as an endogenous inhibitor of tumor angiogenesis and endothelial-cell growth (12). It is one of the most promising anti-angiogenic cancer drugs. It has been successfully radiolabeled with Tc for single photon emission computed tomography (SPECT) imaging of endostatin receptor density in tumors in rats (13). Tc-EC-endostatin may prove to be a useful imaging tracer for selecting patients for anti-angiogenic treatment.