Title page for ETD etd-08012013-105649


Type of Document Master's Thesis
Author Alvarez, Diane
URN etd-08012013-105649
Title Impact of IUdR in Rat 9L Glioma Cell Survival for 25-35 keV Photo-Activated Auger Electron Therapy
Degree Master of Science (M.S.)
Department Physics & Astronomy
Advisory Committee
Advisor Name Title
Hogstrom, Kenneth R Committee Chair
Dugas, Joseph Committee Member
Kurtz, Richard L Committee Member
Matthews, Kenneth L Committee Member
Varnes, Marie Committee Member
Keywords
  • thymidine replacement
  • radiosensitizer
  • SER10
  • IUdR
  • monochromatic x-rays
  • Auger effect
  • synchrotron radiation
Date of Defense 2013-07-16
Availability unrestricted
Abstract
Introduction: Photo-activated Auger electron therapy is a potential technique that could preferentially target cancer cells. This binary therapy uses a drug containing a high-Z element like iododeoxyuridine (IUdR), which serves as a radiosensitizer and molecular carrier of high-Z iodine into cancer cell DNA. Iodine becomes the Auger electron source when activated by photons with an appropriate energy. This work studied the survival of rat 9L glioma cells with IUdR replacing thymidine in the DNA. Irradiations at monochromatic energies above and below the iodine K-edge (33.2 keV) are part of a larger study from 25-70 keV. It was hypothesized that SER10 values for 9% and 18% IUdR-laden 9L glioma cells irradiated by 25-35 keV photons would be greatest at 35 keV due to the Auger effect.

Methods: Rat 9L glioma cells survival versus dose curves with 0%, 9%, and 18% IUdR were measured using four irradiation energies (4 MV x-rays; 35, 30, and 25 keV synchrotron photons). For each of 11 conditions (Energy, %IUdR) survival curves were fit to the data (826 cell cultures) using the linear quadratic model. The ratio of doses resulting in 10% survival gave sensitization enhancement ratios (SER10) from which contributions due to linear-energy transfer (LET), radiosensitization (RS), and Auger effect (AE) were determined.

Results: At 35, 30, and 25 keV, SER10,LET values were 1.080.03, 1.220.02, and 1.370.02, respectively. At 4 MV SER10,RS values for 9% and 18% IUdR were 1.280.02 and 1.400.02, respectively. Assuming LET effects are independent of %IUdR and radiosensitization effects are independent of energy, SER10,AE values for 18% IUdR at 35, 30, and 25 keV were 1.350.05, 1.060.03, and 0.980.03, respectively; values for 9% IUdR at 35 and 25 keV were 1.010.04 and 0.820.02, respectively. Contrastingly, a different, more traditional analysis gave SER10,AE values of 1.270.06 and 1.250.06 at 35 keV for 18% and 9% IUdR, respectively.

Conclusions: Results of this research proved the hypothesis correct; at 35 keV SER10,AE was significantly greater than values at 25 and 30 keV for 18% IUdR and at 25 keV for 9% IUdR. Additional data and radiobiological modeling is required to better explain these results.

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