PURPOSE: Vascular endothelial growth factor-A (VEGF-A) is one of the most important factors inducing angiogenesis in tumors. Nine splice-variant isoforms of VEGF-A have been identified, each having different properties. Recently, we showed that radiolabeled anti-VEGF monoclonal antibody, bevacizumab, accumulates specifically in VEGF-A expressing tumors. In this study, we investigated in a nude mouse model which VEGF-isoforms are responsible for tumor accretion. MATERIALS AND METHODS: The humanized anti-VEGF-A antibody, A.4.6.1. (bevacizumab), was radiolabeled with In-111. The originally VEGF-negative Mel57 tumor was transfected with different VEGF isoforms (VEGF-121, VEGF-165, and VEGF-189). The obtained melanoma xenografts specifically expressing different VEGF-isoforms were used in mice. The bevacizumab uptake was examined in biodistribution studies and by gamma-camera imaging. RESULTS: The tumor cell line expressing VEGF-121 did not show specific uptake, most likely as a result of the fact that this isoform is freely diffusible. Tumors expressing VEGF-165 and -189 were clearly visualized by using gamma-camera imaging. CONCLUSION: The accumulation of radiolabeled bevacizumab in the tumor is due to interaction with VEGF-A isoforms that are associated with the tumor cell surface and/or the extracellular matrix. Scintigraphic imaging of the expression of these VEGF isoforms may thus be useful to predict response to angiogenic therapy.
PURPOSE:Vascular endothelial growth factor-A (VEGF-A) is one of the most important factors inducing angiogenesis in tumors. Nine splice-variant isoforms of VEGF-A have been identified, each having different properties. Recently, we showed that radiolabeled anti-VEGF monoclonal antibody, bevacizumab, accumulates specifically in VEGF-A expressing tumors. In this study, we investigated in a nude mouse model which VEGF-isoforms are responsible for tumor accretion. MATERIALS AND METHODS: The humanized anti-VEGF-A antibody, A.4.6.1. (bevacizumab), was radiolabeled with In-111. The originally VEGF-negative Mel57 tumor was transfected with different VEGF isoforms (VEGF-121, VEGF-165, and VEGF-189). The obtained melanoma xenografts specifically expressing different VEGF-isoforms were used in mice. The bevacizumab uptake was examined in biodistribution studies and by gamma-camera imaging. RESULTS: The tumor cell line expressing VEGF-121 did not show specific uptake, most likely as a result of the fact that this isoform is freely diffusible. Tumors expressing VEGF-165 and -189 were clearly visualized by using gamma-camera imaging. CONCLUSION: The accumulation of radiolabeled bevacizumab in the tumor is due to interaction with VEGF-A isoforms that are associated with the tumor cell surface and/or the extracellular matrix. Scintigraphic imaging of the expression of these VEGF isoforms may thus be useful to predict response to angiogenic therapy.
Authors: Tapan K Nayak; Kayhan Garmestani; Kwamena E Baidoo; Diane E Milenic; Martin W Brechbiel Journal: Int J Cancer Date: 2011-02-15 Impact factor: 7.396
Authors: Neel Patel; Sarah Able; Danny Allen; Emmanouil Fokas; Bart Cornelissen; Fergus V Gleeson; Adrian L Harris; Katherine A Vallis Journal: EJNMMI Res Date: 2017-05-30 Impact factor: 3.434