Lack of effect of SU1498, an inhibitor of vascular endothelial growth factor receptor-2, in a transgenic murine model of retinoblastoma

• Published in: The open ophthalmology journal Vol. 2; no. 1; pp. 62 - 67
• Main Authors: Cebulla, C M, Jockovich, M E, Boutrid, H, Piña, Y, Ruggeri, M, Jiao, S, Bhattacharya, S K, Feuer, W J, Murray, T G
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 02.04.2008
• ISSN: 1874-3641; 1874-3641
• DOI: 10.2174/1874364100802010062

SU1498, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), has activity against retinal neovascular diseases. To determine if this drug might have clinical utility against retinoblastoma, we evaluated the effects of SU1498, as well as the expression of VEGFR-2, in a transgenic animal model of retinoblastoma. Optical coherence tomography (OCT) was evaluated as a technology to measure retinal tumors in vivo, in response to treatment. Immunofluorescence analysis was performed to evaluate the distribution and expression of VEGFR-2 in enucleated eyes from LHbetaTag transgenic mice and controls at 4, 8, 12, and 16 weeks of age. VEGFR-2 and phosphorylated (p)VEGFR-2 levels were quantitated by Western blot. OCT was used to pair 10-week-old animals based on tumor volume (n=10), and these animals were treated with 6 periocular injections of SU1498 (50mg/kg, given twice weekly) or vehicle for 3 weeks. Tumor burden was determined by histology and in vivo imaging by OCT. VEGFR-2 and pVEGFR-2 expression levels were upregulated during tumorigenesis. However, SU1498 did not significantly reduce tumor burden compared to vehicle (p=0.29). OCT imaging of one matched pair demonstrated equivalent, linear tumor growth despite treatment with SU1498. Retinal tumors can be followed non-invasively and quantitatively measured with OCT. VEGFR-2 is strongly upregulated during tumorigenesis in transgenic retinoblastoma; however, SU1498 does not decrease tumor volume in transgenic murine RB at the studied dose and route of administration.