1. Theoretical calculations and simulations of interaction of X-rays with high-Z nanomoities for use in cancer radiotherapy Sara N. Lim, Anil K. Pradhan, Sultana N. Nahar Biophysics Graduate Program Chemical Physics Program Department of Astronomy

2. X-Ray Machines How are medical X-rays produced? Roentgen X-ray tube: Cathode + Anode Electrons Cathode Tungsten Anode X-ray Energy Intensity Bremsstrahlung Radiation Peak Voltage KVp or MVp Imaging devices: Low Energy ~100 KVp – Radiology, CATscanners, etc. Radiation Therapy: High Energy – 6-15 MVp LINAC

3. X-Ray Interaction With High-Z (HZ) Matter: Radiosensitization Compton scattering dominates at high energies, photoionization at low energies Inner-shell ionization  Auger Effect Auger electron emission  localized cell killing HZ Nanovehicles embedded in (tumor) cells X-ray photoionization induces Auger cascades

4. Auger Radiation and Electron cascade Incident photon hits the K-shell Electron absorbs the photon The electron gets ejected, leaving a vacancy The vacancy in the K shell is filled with an L-shell electron, creating a new vacancy The L-shell electron then emits a Kα photon, which can leave as fluorescence, or knock out another L-shell electron We now have 2 vacancies in the L- shell that will be filled with M-shell electrons The two M-shell electrons can emit two photons, which can then knock out two more M- shell electrons This leaves us with four vacancies in the M-shell that will continue this increasing cascade of electron ejection throughout the atom

5. Inner Shell Ionization of HZ Atoms (Gold): Auger Electron Ejections Incident photon knocks out one K- shell electron =80.7keV =13.5keV =2.75keV =0.4kEv =0.009keV =0.053keV That leads to a chain reaction, ejecting more than 20 Auger electrons

6. High-Z Radiosensitization (Gold or Platinum Nanomoities) X-ray beam propagates through body Attenuated by tissue and radiosensitized tumor, located at certain depth in the body Monte Carlo simulations using Geant4 performed, calculating X-ray dose enhancement with respect to low 100-250 keV and high MeV energy X-rays X-ray beam Gold nanoparticle embedded tissue Simulated Water Phantom

7. High Energy MeV X-rays have far lower absorption than low energy keV X-rays P.E. scat. P.E. X-ray absorption coefficients of Platinum and H 2 O P.E. – Photoelectric absorption or photoionization Scat. – Compton scattering Spectra of X-ray devices 100 kVp to 6 MVp Maxima at ~1/3 kVp or MVp High energy LINACs used in radiation therapy produce X-rays mostly at high MeV energies with low P.E. absorption coefficients M L K

8. High vs. Low X-ray energies Conundrum Need high energies for greater penetration in the body to reach the tumor Need low energies for greater absorption by radiaosensitization with high-Z moities LINACS used in radiation therapy ensure sufficient depth but inefficient for radiosensitization

9. Photoionization, Auger decays and malignant cell-killing therapeutics 160 kV Investigate low energy source 160 KVp, and high energy LINAC 6 MVp Simulate tumor at depth of 10 cm in water phantom, sensitized with Pt at two different concentrations: 1.0 mg/g and 7.0 mg/g P.E. absorption from low energy 160 kV source is more than an order of magnitude higher than the 6 MV source (LINAC) with change in concentration LINAC high energy X-rays are largely Compton scattered instead of photoionization and Auger decays; not much dependence on Pt concentration Photoabsorption vs. Depth in water phantom 6 MV Pt sensitized tumor at 10 cm

10. X-ray absorption with depth of radiosensitized tumor and energy PhotoionizationTotal (photo + Scatt) Low energy 160 kV X-rays have much higher absorption than high energy 6 MV X-rays

11. Dose Enhancement Factors (DEF): X-ray Dose absorbed w and w/o Pt X-ray dose deposition as a function depth, 7ug/ml Pt at 10 cm in water phantom Integrated DEF over the entire tumor volume; decreases with incident X-ray energy 160 kV 6 MV

12. Single Cell Dose Enhancement Factors In Gold (Au) and Gadolinium (Gd)

13. Dose Deposition per photon (in single cell) 80 keV 5 MeV

14. What about bone? Nightmare Before Christmas. Henry Selick, Tim Burton, Michael McDowell, Caroline Thompson. Walt Disney Studios, 1993. Bone (calcium) absorption of X- rays is higher than water (muscle, fat) How is radiosensitization affected in tissue covered with bone ? Radiation therapy of brain tumors!

15. Brain (+Skull) Dose Enhancement At Low KeV and High MeV Energies Greater dose to skull (~ 2.5 X for 80 keV), BUT! dose to normal brain HALVED Dose to sensitized tumor less but comparable Normalized X-ray dose 1 Joule

16. Conclusion and Follow On Efficient radiation therapy using high-Z compounds requires low-energy X-rays Next talk by Sara Lim -- In vitro and in vivo experiments -- HZ radiosensitization with low energy (keV) and high energy (MeV) X-rays