Abstract 1570: Thermal ablation improves oxygenation in remaining viable tumor

To increase the use and effectiveness of thermal therapy of various solid cancers, it is necessary to understand how tumor remaining viable after ablation responds and repairs. Tumor oxygenation and angiogenesis are critical for tumor recurrence and therefore we are studying the changes in tumor oxygenation and migration pattern of endothelial progenitor cells (EPCs), one component of angiogenesis, after local thermal ablation of tumors in mice. Tumor cells in sublethal ablation zones may release a unique set of chemokines in an attempt to attract cells to repair and regrow the tumor. The location and mechanisms by which these cells are recruited to the tumor may be distinct from other methods of thermal therapy which suggests that specific targets to improve ablation outcomes may be identified. If the oxygenation is changed in tumor that remains viable after ablation, concomitant application of chemotherapy or radiation therapy may be an effective way to improve tumor control. Murine FSaII fibrosarcoma and 4T1 breast carcinoma tumors were ablated with a conductance probe or high intensity ultrasound at an average peak temperature of 60-90C for 1.5 min. One group of mice was immediately injected IV with near infrared emitting indocyanine green (ICG)-labeled EPCs, while the other group was injected with EPCs labeled with a stable in situ dye (PKH). The mice injected with ICG-labeled EPC were optically imaged at various time points up to 72 hours. These images were then compared to those of untreated tumors to observe the migration patterns of EPC in mice that had received HIFU ablation. In other mice, pimonidazole was injected 72 h post ablation and tumors were excised and stained for pimonidazole adducts as evidence of hypoxia. We routinely ablated approximately 50% of tumor tissue, leaving the other 50% peripheral tumor tissue viable. We were able to detect an increased amount of ICG signal in the tumor that received ablation ablation, when compared to controls. Histological examination revealed the presence of EPC cells in the tumor after ablation, while the control showed no signs of EPC presence. The tumor oxygenation in viable tissue after ablation was found to increase from control tumors where 27% of the tumor was pimonidazole positive to only 5% in thermally ablated tumors. The role of endothelial progenitors and tumor oxygenation changes in overall tumor response to ablation alone and combined with other modalities is being actively studied by our