Abstract 4913: Development of Fe3O4@TiO2 core-shell nanocomposites as radiosensitizers
Authors: Refaat Tamer , West Derek , Harris kathleen R. , Parini Vamsi , Liu William , Wanzer Beau , Finney Lydia , Larson Andrew C. , Bautista Jonathan , Sathiaseelan Vythialinga , Mittal Bharat , Paunesku Tatjana , Woloschak Gayle 
Published: May 2015

Abstract
Purpose: To test in vivo, in a rabbit VX2 liver cancer model, a nanocomposite made with Fe3O4 core and TiO2 shell as a possible radiosensitization agent.
Methods: This study was approved by the institutional ACUC. Rabbits were implanted in liver with pairs of VX2 tumors distantly enough to allow irradiation of only one of the two tumors. The tumors were allowed to grow until clearly detectable by magnetic resonance imaging, followed by Computed Tomography (CT) simulation to identify and contour the tumors. Each rabbit was anesthetized, and immobilized in supine position. Isocenter was placed during the CT simulation and the rabbit was tattooed. After the CT, each rabbit was injected with nanoparticles and put under observation until recovery. The core-shell nanoparticles were surface covered with glucose (glut-NPs) and delivered intravenously to 6 rabbits. A radiation oncologist contoured the target volumes. The gross target volume included a hepatic tumor in one lobe; 1 - 3 mm expansion was done to create the clinical target volume and another 1-2 mm expansion to create the planning target volume (PTV). The control hepatic tumor was contoured and the treatment plan objective was to deliver more than 95% of the prescribed dose to the PTV while sparing the control tumor. A certified radiation physicist created the treatment plan. Dose Volume Histograms were created and the radiation oncologist approved the plan. Irradiation usually utilized 2 - 3 beams, delivering 2 Gy as a single fraction using Linear Accelerator. All 6 rabbits treated with nanoparticles the day before (14-18h previously) and 3 radiation-only (not glut-NPs treated) animals were irradiated so that only one of the tumors received radiation. The animals were terminated 3 days after irradiation and the tumors were harvested. Several view-fields with at 3-10 x 103 cells were automatically scored using the NanoZoomer and percentage of Ki67 positive cells, as a marker of proliferation was determined in each tumor. TUNEL assay was done as well.
Results: In each rabbit the larger tumor of the pair was irradiated. In no-NP treated animals that led to the fact that irradiated tumors at 3 days after irradiation generally still had greater number of proliferating cells than the non-irradiated tumor sections. Conversely, in glut-NPs treated rabbits, irradiation led to a decrease of Ki-67 positive cells compared to the paired non-irradiated glut-NPs treated tumors. Three-day time-point was better suited for evaluation of tumor proliferation changes. TUNEL analysis showed higher apoptotic cell numbers in glut-NPs treated tumors (p=0.049). Combination of radiation with glut-NP treatment showed only a mild trend for increased apoptosis compared to non-irradiated glut-NPs treated tumors, this trend was not statistically significant (p=0.53).
Conclusion: These data suggest that the glut-NPs show a considerable promise for radiosensitization.
Note: This abstract was not presented at the meeting.
Citation Format: Tamer Refaat, Derek West, kathleen R. Harris, Vamsi Parini, William Liu, Beau Wanzer, Lydia Finney, Andrew C. Larson, Jonathan Bautista, Vythialinga Sathiaseelan, Bharat Mittal, Tatjana Paunesku, Gayle Woloschak. Development of Fe3O4@TiO2 core-shell nanocomposites as radiosensitizers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4913. doi:10.1158/1538-7445.AM2014-4913