Computational and experimental evaluation of absorbed doses in gold nanoparticles mediated contrast enhanced radiotherapy for tumor-bearing laboratory animals

Contrast-enhanced radiotherapy (CERT) is a method of radiation therapy based on the interaction of a dose-enhancing agent with external X-ray radiation. Gold nanoparticles are a promising dose-enhancing agent. The aim of the work is to determine the maximum concentration of gold and corresponding dose enhancement factor (DEF) in healthy organs and tumor node after intravenous injection of nanoparticles to tumor-bearing mice, according to computed tomography data. Mice with subcutaneous syngeneic tumors were used for the study: melanoma B16F10 (n=5); adenocarcinoma Ca755 (n=5); EMT6 (n=5); 4T1 (n=5). Laser-ablated gold nanoparticles with a diameter of 8.3 nm were injected intravenously to mice at a dosage of 1000 mg Au/kg body weight. computed tomography scans were acquired before nanoparticle injection, then immediately after injection and after 1, 4, 24, 48 h and 5 days. Using a linear calibration relationship, the increase in tissue radiodensity was recalculated into the concentration of gold. The local increase in the absorbed dose was estimated using the analytical dependence of DEF on the concentration of gold nanoparticles for X-rays with a maximum energy of 140 kV. The maximum concentration of gold in the tumor was determined for 4 tumor models. The calculated DEF ranged from 1.3+/-0.2 for B16F10 melanoma to 1.60.2 for 4T1 adenocarcinoma. At 48 h after injection, there were also high concentrations of gold in blood (DEF for heart wall from 1.5+/-0.2) and in liver tissue (DEF from 1.4+/-0.1). 4T1 adenocarcinoma is an optimal tumor model for further in vivo studies of CERT. High concentration of gold in heart chambers and in liver tissue limits the application of CERT for lung, mediastinal and abdominal tumors. CERT is most applicable for tumors of brain and extremities.