Recent studies from our group and others demonstrated that the in vivo apoptotic damage delivered by SDRT to endothelial compartment is critical for SDRT-induced tumor cure, whereas angiogenesis factors (VEGF, FGF etc.) partially reversed this effect [6, 13, 14]. We showed above that Pazopanib enhanced SDRT effect in two human sarcoma tumor models. Next, we determined the effect of the combined therapies on the vasculature. First, we evaluated TEC apoptosis at 6 h post-radiation. JJ012 and MNPST3 tumors were pre-treated with Pazopanib (−1 h, 100 mg/kg p.o.) and irradiated with 15 Gy or 30 Gy accordingly. As shown in Figure 2A and 2B, compared to a baseline TEC apoptosis in non-treated control JJ012 tumors (8.8 ± 2.1%) and MNPST3 tumors (6.1 ± 1.2%), Pazopanib alone generated a modest increase of TEC apoptosis in JJ012 (13 ± 5.6%) and in MPNST3 (12.2 ± 3.2%). While SDRT alone triggered a significant increase in TEC apoptosis (18 ± 3% in JJ012 tumors and 15.7 ± 2.6% in MPNST3 tumors), in the combination treatment with Pazopanib and SDRT there was a further increase in the TEC apoptosis (26.7 ± 2.7% in JJ012 tumors and 21.3 ± 2.3% in MPNST3 tumors), which was significantly higher than each treatment alone. These observations indicated that the combination of Pazopanib and SDRT significantly increased TEC apoptosis in human sarcoma animal models when Pazopanib is administered 1 h before radiation.