M. Meser Ali PhD, Abstract Co-Author: Nothing to Disclose

Branislava Janic PhD, Abstract Co-Author: Nothing to Disclose

Abbas Babajani-Feremi PhD, Abstract Co-Author: Nothing to Disclose

Asm Iskander MBBS, Abstract Co-Author: Nothing to Disclose

Nadimpalli Ravi Sankara Varma PhD, Abstract Co-Author: Nothing to Disclose

Syed Arbab Ali MD, PhD, Presenter: Nothing to Disclose

Very recently, vascular endothelial growth factor receptors (VEGFR) tyrosine kinase  inhibitor (Vetanalib/PTK787) has been used in glioma patient in conjunction with chemotherapy and radiotherapy but results are yet to be published. However, changes in the tumor size, tumor vascular permeability, vascular density, expression of VEGFR2, and changes in other angiogenic factors are not well documented following the treatment with Vetanalib. The purposes of this study were to determine the tumor size, vascular permeability, distribution volume, and expression of VEGFR2 in treated and non-treated implanted glioma (U-251) by in vivo MRI and SPECT. The findings were compared and correlated with histochemical and western blotting studies.

Groups of rats carrying intracranial glioma (U-251) were subjected to treatment with either PTK787 or vehicles-only for two weeks. The treatment was started 7 days after the implantation of tumor cells. Following the treatment; tumor size, tumor vascular permeability transfer constant (Ktrans), distribution volume (FV), and expression of VEGFR2 were determined by in vivo MRI and SPECT studies (Tc-99-HYNIC-VEGF-c). Following imaging studies, animals were sacrificed and tumors as well as contralateral brain were collected for histochemistry and western blotting studies to determine different angiogenic factors and receptors related to angiogenesis.

DCE-MRI using a high molecular weight (MW) contrast agent (albumin-(GdDTPA) showed significantly increased Ktrans at the rim of the treated tumor compared to that of the central part of the treated as well as untreated tumors. Size of the tumors was also increased in treated group. Tc-99m-HYNIC-VEGF-c SPECT showed significantly increased activity at the treated tumors. In PTK-treated tumors, histological staining revealed increase in tumor proliferative activity and microvessel density in the close proximity to the tumor border. Western blotting study indicated increased VEGFR2 expression at the peripheral part of the treated tumors compared to that of vehicle-treated and central part of the treated tumors.

These findings indicate that PTK treatment induced over expression of VEGF as well as the VEGFR2 especially at the rim of the tumor as proven by DCE-MRI, SPECT imaging and immunohistochemistry.

Anti-angiogenic treatment targeting VEGF receptors may not be effective agaisnt malignant glioma

Ali, M, Janic, B, Babajani-Feremi, A, Iskander, A, Varma, N, Ali, S, Changes in Vascular Permeability and Expression of VEGFR2 Following Anti-angiogenic Treatment in Rat Gliom: MRI and SPECT Studies.  Radiological Society of North America 2009 Scientific Assembly and Annual Meeting, November 29 - December 4, 2009 ,Chicago IL. http://archive.rsna.org/2009/8003608.html