Vascular Growth Factor Receptors as a Target for Auger Electron Radiotherapy of Breast Cancer.

摘要

Breast tumor is a aggressive and highly vascularized tumor in which angiogenesis is necessary to support growth.. Vascular endothelial growth factor (VEGF) is secreted by breast cancer cells(2) to stimulate angiogenesis through the over-expression of its receptors (VEGFR1 & 2) and proliferation of the vascular endothelial cells (VEC) of the surrounding tissue. In contrast, normal VECs express low level of VEGFRs. Strategies for targeting VEGFR to inhibit growth of breast cancer(3-5) have been tested, but had limited success. On binding to its receptors, VEGF is internalized via the receptor mediated endocytosis pathway way to the endosomal compartment of the endothelial cells. Our preliminary data using fluorescein-conjugated VEGF(165) showed that it was internalized into cytoplasmic vesicles inside human umbilical vein endothelial cells (HUVEC) (left panel A) and translocated to near the nucleus which formed a ring of fluorescence surrounding the nucleus (left panel B). Therefore, the aim of the present project is to target the overexpressed VEGFRs on the endothelial cells of the breast tumor, to deliver lethal levels of Auger electron emitting radionuclide Indium-(111) (In111) into breast cancer associated VECs which could be an effective radiotherapy for breast cancer.