[Angiogenesis in cancer and its detection with radiolabeled biomolecules].
The present article refers to the mechanism of angiogenesis, a phenomenon which in certain cases is normal, however it usually accompanies the formation of solid cancerous tumors. During the process of angiogenesis, migration, differentiation and proliferation of endothelial cells occurs. In some pathological cases, the most important of which is cancer, the mechanism of angiogenesis is reinforced. It has been observed that a tumor cannot grow without the formation of new blood vessels in the surrounding tissues, which account for blood supply to the tumor. The process of angiogenesis is regulated by chemical signals of the organism, which function as an "angiogenesis switch" regulating the formation of new vasculature. A variety of anti-angiogenic agents which lead to angiogenesis inhibition are found in the clinical trial phase. Among these agents are: i) molecules which inhibit the action of Vascular Endothelial Growth Factors, VEGF, ii) molecules which obstruct migration, differentiation and proliferation of endothelial cells, via their binding to receptors of the alpha(nu)beta(3) integrins and iii) inhibitors of metalloproteinases (MMP). Certain molecules of the above mentioned categories, labeled with radionuclides which emit gamma- radiation or beta- particles or positrons, have been proposed and are being evaluated as possible radiopharmaceuticals, for the visualization of receptors involved in the mechanism of angiogenesis, aiming at the scintigraphic detection of primary or metastatic cancer at an early stage and possibly, aiming at its inhibition/treatment. Regarding the study of angiogenesis the following have been described: a. antibodies targeting VEGF, labeled with radionuclides emitting beta- and/or gamma-radiation, which can be applied for the diagnosis and possibly, for the treatment of cancer, b. peptide derivatives which contain the amino-acid sequence RGD (Arg-Gly-Asp) and compete for the alpha(nu)beta(3) integrins, with the proteins of the stroma. It has been found that these radiolabeled derivatives localize in tumors and can be used for the visualization and, possibly, for the tumor eradication of primary and metastatic cancer.
Psimadas
Dimitrios
D
Institute of Radioisotopes-Radiodiagnostic Products, N.C.S.R. "Demokritos", Agia Paraskevi Attikis, 153 10 Athens, Greece. dpsimad@chem.uoa.gr.
Bouzioti
Pinelopi
P
D000818:Animals; D000911:Antibodies, Monoclonal; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000150:complications / Q000000981:diagnostic imaging*; D009389:Neovascularization, Pathologic / Q000150:complications / Q000000981:diagnostic imaging*; D009842:Oligopeptides; D011868:Radioisotopes; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
D000911:Antibodies, Monoclonal; D009842:Oligopeptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; C047981:arginyl-glycyl-aspartic acid