1. Superiority of 160 kV vs 6 MV X- ray irradiation combined with heavy element radiosensitization By: Sara N. Lim, Anil K. Pradhan, Sultana N. Nahar, Rolf F. Barth, Claudia Turro, Alycia M. Palmer, Erica H. Bell and Xiaokui Mo

2. Outline of presentation Background: X-ray radiotherapy and how can we improve it? Low energy 160 kV vs 6000 kV (6 MV) X-rays What is radiosensitization? enhancing X-ray dose with heavy elements to kill malignant cells Monte Carlo simulations on radiosensitization using heavy elements (high atomic number Z or HZ – review from earlier presentation). Experiments: promising in vitro results In vivo experiments in progress

3. Current Radiotherapy 6 MV clinical linac (Varian Clinac) unfiltered spectrum: ~0-6000 keV (6 MeV) X-rays can not differentiate between tumor tissues and healthy tissues with or with out radiosensitization Reason for use: penetration

4. What if there was a way to increase the damage to tumor tissues that more than makes up for the lack of penetration? There is! With heavy element radiosensitization!

5. Dose Enhancement Factors Geant4 results using 7ug/ml Pt for increase in dose deposition as a function of X-ray energy 160 kV 6 MV

6. In vitro experiments F98 rat glioma cells: Radiosensitized with relatively non- toxic HZ radiosensitizer or carboplatin Irradiated with either 6 MV or 160 kV X- rays to test changes in surviving fraction (SF)

7. In vitro analysis Methods and materials Clonogenic assay with Pt-sensitized F98 cells after broadband X-ray irradiation (160 kV Vs 6 MV, 7 Gy) 1. 2. Radiosensitizers: Pyridine Terpyridine Pt(II) complex (typ-Pt) - low in vitro toxicity - allows decoupling of chemotoxicity and radiotoxicity - unexpectedly cytotoxic in vivo Carboplatin - common cancer therapeutic – well known cytotoxic range - going to be used in in vivo study

8. Decrease in malignant cell survival after irradiation varying amounts of radiosensitizer no x-ray 6 MV 160 kV no x-ray 6 MV 160 kV

9. Increase cell killing: Low Energy VS High Energy 160 kV 6 MV radiation dose

10. Decrease in malignant cell survival after irradiation varying radiation dose (with carboplatin) No sig. difference

11. In vivo experiments Non – therapeutic dose of carboplatin 10 3 F98 glioma cells 160 kV 10 Gy 6 MV 10 Gy So, what will this experiment show?

12. In vivo experiments Stay tuned for the sequel

13. Conclusion In vitro experiments showed greater cell death with low energy X-rays Radiosensitized rats treated with low energy X- rays SHOULD live longer

14. Thanks for listening!