Program Information
Modulation of Clinical Orthovoltage X-Ray Spectrum Further Enhances Radiosensitization of Cancer Cells Targeted with Gold Nanoparticles
T Wolfe*, F Reynoso , J Cho , C Quini , M Cortez , N Manohar , S Krishnan , S Cho , UT MD Anderson Cancer Center, Houston, TX
Presentations
MO-FG-BRA-2 (Monday, July 13, 2015) 4:30 PM - 6:00 PM Room: Ballroom A
Purpose: To assess the potential to amplify radiosensitization of cancer cells targeted with gold nanoparticles by augmenting selective spectral components of X-ray beam.
Methods: Human prostate cancer cells were treated for 24h with gold nanorods conjugated to goserelin acetate or pegylated, systematically washed and irradiated with 250 kVp X-rays (25mA, 0.25mm Cu-filter, 8x8cm² field size, 50cm SSD) with or without an additional 0.25 mm Erbium (Er) filter. As demonstrated in a companion Monte Carlo study, Er-filter acted as an external target to feed Erbium K-shell X-ray fluorescence photons (~50 keV) into the 250 kVp beam. After irradiation, we performed measurements of clonogenic viability with doses between 0-6Gy, irreparable DNA damage assay to measure double-strand breaks via γH2AX-foci staining, and production of stable reactive oxygen species (ROS).
Results: The clonogenic assay for the group treated with conjugated nanoparticles showed radiosensitization enhancement factor (REF), calculated at the 10% survival fraction aisle, of (1.62±0.07) vs. (1.23±0.04) with/without the Er-filter in the 250 kVp beam, respectively. The group treated with pegylated nanoparticles, albeit retained in modest amounts within the cells, also showed statistically significant REF (1.13±0.09) when the Erbium filter was added to the beam. No significant radiosensitization was observed for other groups. Measurements of ROS levels showed increments of (1.9±0.2) vs. (1.4±0.1) for combined treatment with targeted nanoparticles and Er-filtered beam. γH2AX-foci showed 50% increase for the same treatment combination, confirming the enhanced radiosensitization in a consistent fashion.
Conclusion: Our study demonstrates the feasibility of enhancing radiosensitization of cancer cells by combining actively targeted gold nanoparticles and modulating the X-ray spectrum in the desired energy range. The established technique will not only help develop strategies to maximize nanoparticle-mediated radiosensitization but also offer a convenient way to acquire unprecedented insights into the role of photon energy for the observed radiosensitization effects.
Funding Support, Disclosures, and Conflict of Interest: Supported by DOD/PCRP grant W81XWH-12-1-0198
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