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Monte Carlo Evaluation of Dose Enhancement Due to CuATSM Uptake in Hypoxic Environments with External Radiation

S Martinez1*, D Leary2 , (1) Colorado State University, Cheyenne, Wy, (2) Colorado State Univ, Fort Collins, CO


(Thursday, 8/2/2018) 1:00 PM - 3:00 PM

Room: Karl Dean Ballroom A1

Purpose: Most solid tumors contain areas of chronic hypoxia caused by limited diffusion of oxygen from tumor microvasculature. In recent years gold nanoparticles (GNP) have been explored for their potential as an enhancer of external beam radiation, however GNP have lower cellular uptake in anoxic and hypoxic conditions. The chelator diacetylbis(N(4)-methylthiosemicarbazonato) copper II (CuATSM), used in PET hypoxic imaging provides potential to overcome the hypoxic barrier by preferentially depositing copper into tumor regions previously inaccessible regions.

Methods: Three external beam sources were modeled with EGSnrc. Each had a different spectra in the orthovoltage (225kVp), MV imaging (2.35MV), and conventional MV treatment (6MV) range to determine the efficacy of radio-enhancement from each source. Inhomogeneous regions, varying in realistic concentrations of either copper or gold, were simulated to determine deposited dose. Additionally, lateral scatter contribution to the central axis was determined by varying the size of the inhomogeneity perpendicular to the beam path.

Results: Physical dose enhancement was preferentially increased for beam spectra with low energy photons, and was highly concentration dependent between 0.1mg/kg to 100g/kg. Small dose enhancements between 0.14 and 0.42 were found in the tumor model for commonly used diagnostic doses of CuATSM. However, by increasing this dose to high but sub-toxic levels much higher dose enhancement factors were realized from 1.6 up to 19.0. Additionally, depth of inhomogeneity had an effect up to 2x on dose escalation between 1cm and 6cm that was more pronounced for low energy photon spectra.

Conclusion: Hypoxic regions of tumors are highly radio-resistant and difficult to alter using pure metal radio-sensitizers. CuATSM presents an opportunity to target hypoxic regions with metal radio-sensitizers by the nature of its ability to deposit in reduced tissue. CuATSM at high concentrations with low energy photons has some efficacy for enhancing dose in hypoxic tumor regions.


Modeling, Radiosensitivity, Hypoxia


TH- External beam- photons: Monte Carlo

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