Angiostatic kinase inhibitors to sustain photodynamic angio-occlusion

Targeted angiostatic therapy receives major attention for the treatment of cancer and exudative age-related macular degeneration (AMD). Photodynamic therapy (PDT) has been used as an effective clinical approach for these diseases. Since PDT can cause an angiogenic response in the treated tissue, combination of PDT with anti-angiogenic compounds should lead to improved therapy. The current study was undertaken to test the clinically used small molecule kinase inhibitors Nexavar(®) (sorafenib), Tarceva(®) (erlotinib), and Sutent(®) (sunitinib) for this purpose, and compare the results to the combination of Visudyne(®)-PDT with Avastin(®) (bevacizumab) treatment. When topically applied to the chicken chorioallantoic membrane (CAM) at embryo development day (EDD) 7, a clear inhibition of blood vessel development was observed, with sorafenib being most efficient. To investigate combination with phototherapy, Visudyne(®)-PDT was first applied on EDD11 to close all