Radiolabeled biomolecules for early cancer detection and therapy via angiogenesis targeting

Abstract Tumors cannot grow or metastasize without the formation of new blood vessels, i.e. without angiogenesis. A variety of anti-angiogenic agents leading to angiogenesis inhibition are in the clinical trial phase, among which are: (i) molecules which inhibit the action of Vascular Endothelial Growth Factors, VEGF and (ii) molecules which obstruct migration, differentiation and proliferation of endothelial cells, via their binding to receptors of the α ν β 3 integrins. Certain derivatives of the abovementioned categories, labeled with radionuclides, which emit γ-radiation or β-particles or positrons, have been proposed and are being evaluated as possible radiopharmaceuticals, for the detection and/or treatment of primary or metastatic cancer at an early stage. For the study of angiogenesis the following have been described: (a) antibodies targeting VEGF, labeled with radionuclides emitting β- and/or γ-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 α ν β 3 integrins, with the proteins of the stroma. It has been found that these radiolabeled biomolecules localize in tumors and can be used for the visualization and, possibly, for tumor eradication of primary and metastatic cancer. In our laboratory radiolabeling of biomolecules by beta and/or gamma emitters is a principal research goal. In the present work we are presenting our results on the labeling of monoclonal antibodies and peptides with β- and γ-emitting isotopes, as well as on their in vivo evaluation in experimental animal models, by use of specially dedicated imaging devices.