Figure 4.

Radiosensitization of orthotopic U1242/luc-GFP tumors with KU-60019. Athymic female mice were implanted with U1242/luc-GFP cells. Osmotic pumps (ALZET M2002) were filled with KU-60019 or PBS, connected to a cannula (Brain infusion kit 3; ALZET), inserted in the skull at a depth of 3 mm at the site of cell injection, and the pump placed under the skin on the back of the mouse. The M2002 pump delivers the drug at a rate of 0.5 μl/hr over 14 days. A, Mice with tumors were imaged by BLI 7 days post-cell injection followed by pump implantation with KU-60019 (10 μM) (+KU) or not (-KU). Tumor growth was determined at 13 days by BLI followed by 2 Gy of cranial irradiation to both mice. Seven days later (day 20) mice were imaged by BLI, euthanized, and the brains removed for GFP imaging using Caliper IVIS-200. Tumor was evident in the brain receiving radiation alone, but not in the brain receiving KU-60019 and radiation. B, Radiosensitization of U1242/luc-GFP tumors with KU-60019 delivered by intra-tumoral osmotic pump. Cells were injected followed by implantation of osmotic pumps as in (A) except that pumps (ALZET M1007D) were inserted 7 days after cell implantation and irradiation (single dose of 5 Gy) was done 7 days (day 14) later. Tumor growth was monitored by BLI. Two mice (A51 and A53), in the KU-60019 and radiation group that survived for >200 days and were apparently healthy when euthanized. Mean survival: no treatment; 27 ± 4 days (N = 5), 5 Gy; 34 ± 1 days (N = 5), KU-60019; 35 ± 4 days (N = 4), and KU-60019 + 5 Gy; 109 ± 94 days (N = 5). A significant 75 day growth-delay between the KU-60019 and radiation and radiation alone groups was noted (P = 0.00402 vs. all treatments).