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Molecular-Targeted Gold Nanorods Enhances the RBE of Proton Therapy

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P Diagaradjane

A Khoo , N Sahoo , S Krishnan , P Diagaradjane*, UT MD Anderson Cancer Center, Houston, TX


SU-F-T-666 (Sunday, July 31, 2016) 3:00 PM - 6:00 PM Room: Exhibit Hall

Purpose:In recent years, proton beam radiation therapy (PBRT) has gained significant attention in the treatment of tumors in anatomically complex locations. However, the therapeutic benefit of PBRT is limited by a relative biological effectiveness (RBE) of just 1.1. The purpose of this study is to evaluate whether this limitation can be overcome by artificially enhancing the RBE using molecular-targeted gold nanorods (GNRs).

Methods:Molecular-targeting of GNRs was accomplished using Cetuximab (antibody specific to epidermal growth factor receptor that is over-expressed in tumors) conjugated GNRs (cGNRs) and their binding affinity to Head and Neck cancer cells was confirmed using dark field microscopy and Transmission Electron Microscopy (TEM). The radiosensitization potential of cGNRs when irradiated with photon (6MV) and proton (100 and 160 MeV) beams was determined using clonogenic assays. The RBE at 10% surviving fraction (RBE₁₀) for proton therapies at central and distal locations of SOBP was calculated with respect to 6 MV photons. IgG-conjugated GNRs (iGNRs) were used as controls in all experiments.

Results:cGNRs demonstrated significant radiosensitization when compared to iGNRs for 6MV photons (1.14 vs 1.04), 100 MeV protons (1.19 vs 1.04), and 160 MeV protons (1.17 vs 1.04). While RBE10 for proton beams at the center of SOBP revealed similar effects for both 100 and 160 MeV (RBE₁₀=1.39 vs 1.38; p>0.05), enhanced radiosensitization was observed at the distal SOBP with 100 MeV beams demonstrating greater effect than 160 MeV beams (RBE₁₀=1.79 vs 1.6; p<0.05).

Conclusion:EGFR-targeting GNRs significantly enhance the RBE of protons well above the accepted 1.1 value. The enhanced RBE observed for lower energy protons (100 MeV) and at the distal SOBP suggests that low energy components may play a role in the observed radiosensitization effect. This strategy holds promise for clinical translation and could evolve as a paradigm-changing approach in the field of radiation oncology.

Funding Support, Disclosures, and Conflict of Interest: The UT MD Anderson Cancer Center's Institutional Research Grant funding to P. Diagaradjane

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