Abstract No. 540 Correlations of Ionizing Radiation to Histopathologic Changes and Long-Term Biological Effects of Radiation

To evaluate histopathologic changes after 90Y transarterial radioembolization (TARE) and determine a potential correlation of radiation dose to cancer cell death. 13 colorectal liver metastasis (12 patients) treated with 90Y TARE were evaluated through image-guided core biopsy in a prospective study. Tissue core sampling was obtained immediately T0 (within 3 hours) and 3 weeks after TARE (T3). Biopsy samples were evaluated with hematoxylin-eosin, Ki67, OxPhos antibody, TUNEL assay, caspase-3 (CC3), and pH2AX for double-strand DNA breaks (DSB). Ki67 and PH2AX immunolabeling was evaluated quantitatively to see the correlation of tissue changes with tissue exposure to radiation (TRD). DSB was detected in all samples ranging 75%-100% at T0. There was no linear correlation between TRD and the percentage of DSB. DSB persisted at T3 ranging between 6.96%-75.85%. A down-regulation of the Ki-67 antigen was documented at T0 and T3 post TARE. OxPhos and Tunnel assays did not show any correlations. A correlation between post TARE CC3 activation and tumor progression was observed. CC3 activation was noted in 6 of 7 cases that progressed within 4 months post TARE. A potential correlation of post-TARE CC3 activation with tumor progression deserves further exploration for the development of early tissue biomarkers of response to TARE. Preliminary results show that DSB may not be a reliable quantification biomarker of TARE induced cellular damage.