MO‐FG‐BRA‐02: Modulation of Clinical Orthovoltage X‐Ray Spectrum Further Enhances Radiosensitization of Cancer Cells Targeted with Gold Nanoparticles

Abstract

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.Supported by DOD/PCRP grant W81XWH‐12‐1‐0198