ABSTRACT
BACKGROUND: Angiogenesis is the development of new blood vessels from pre-existing ones. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic activators. Our studies are focused on the detection of VEGF by use of radiolabeled anti-endothelial monoclonal antibodies, which have the ability to localize in newly-formed vasculature of a cancerous origin. MATERIALS AND METHODS: The anti-endothelial monoclonal antibody VG76e was labeled with Samarium-153 and Technetium-99m. Biodistribution of the radiolabeled species was assessed in normal female Swiss mice, while tumor uptake was also evaluated. RESULTS: VG76e was labeled with 99mTc and 153Sm, resulting in a single product with a labeling yield of over 95%. Biodistribution studies showed non-specific uptake in any organ, with elimination via the hepatobiliary system. Finally, satisfactory tumor uptake was observed for both radiolabeled derivatives. CONCLUSION: Monoclonal antibodies raised against epithelial growth factors or their receptors, when labeled with appropriate radionuclides, may be a useful tool for early tumor detection and eventually for therapy.
Subject(s)
Antibodies, Monoclonal/pharmacokinetics , Breast Neoplasms/diagnostic imaging , Immunoconjugates/pharmacokinetics , Neovascularization, Pathologic/diagnostic imaging , Radioisotopes/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , Samarium/pharmacokinetics , Technetium/pharmacokinetics , Animals , Antibodies, Monoclonal/therapeutic use , Breast Neoplasms/blood supply , Breast Neoplasms/metabolism , Female , Humans , Immunoconjugates/therapeutic use , Isotope Labeling , Mice , Mice, Nude , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/radiotherapy , Radioisotopes/therapeutic use , Radionuclide Imaging , Radiopharmaceuticals/therapeutic use , Samarium/therapeutic use , Technetium/therapeutic use , Tumor Cells, CulturedABSTRACT
In a large study of chromosome rearrangements occurring in human lymphocytes from normal subjects, inv (14)(q12qter) or (q11.2q32.3) is found to be the most frequent, affecting 0.15% of mitoses. The same inversion is observed in the lymphocytes of the chimpanzee, indicating the ancestry of this inversion. It is not induced by ionizing radiations, and its frequency may be increased in Fanconi anemia, but not in ataxia telangiectasia. It may represent one of the steps of the process of leukemogenesis.