title: Monte Carlo study of the dose enhancement effect of gold nanoparticles during X-ray therapies and evaluation of the anti-angiogenic effect on tumour capillary vessels.
abstract: Gold nanoparticles (GNPs) are a promising radiosensitizer agent in radiotherapy. Through a simulation performed with the Geant4 Monte Carlo code, we evaluated the dose enhancement effect of GNPs during therapies with an x-ray tube operating at 150 kV (E = 55 keV and E(max) = 150 keV) and we studied the impact of GNP diffusion out of the tumour vessels, in terms of antiangiogenic and cytotoxic effects. Firstly, a single x-ray beam was assumed to irradiate a parallelepiped volume of soft tissue, in which a GNP-doped "target" volume was placed at different depths. Average dose enhancement factors (DEF) in presence of GNPs were obtained as a function of the target depth and GNP concentration, uniformly distributed; values ranging between 1.6 for 10 mg Au/g at 0 cm and 7.2 for 200 mg Au/g at 5 cm were determined. Furtherly, a second geometry was adopted, in which a blood capillary vessel (10 μm thick and 10 μm of inner radius) was placed at the centre of a cubic volume of soft tissue; doses and DEFs to the capillary endothelium as well as to the surrounding viable tumour were evaluated, for different models of GNP diffusion. Our results indicate that the radial DEF profiles around the vessel are in close relationship with the radial profiles of GNP concentration assumed, except for at sharp gradients of concentration. DEFs at the endothelium ranged from 1.6 to 6.5, for GNP concentrations in the blood of 10 and 200 mg/ml, respectively. These data can be helpful for the development of new and more specific GNP-based radiosensitizers of potential interest in radiotherapy, exploiting the combined benefit of anti-angiogenic and cytotoxic dose enhancement effects.
authors.affiliation: Section of Radiological Sciences, Department of Biomedical Sciences and of Morphologic and Functional Imaging, University of Messina, Messina, Italy. eamato@unime.it
authors.forename: Ernesto
authors.initials: E
authors.lastname: Amato
authors.forename: Antonio
authors.initials: A
authors.lastname: Italiano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Leotta
authors.forename: Stefano
authors.initials: S
authors.lastname: Pergolizzi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Torrisi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D003198:Computer Simulation; D004058:Diffusion; D042783:Endothelial Cells / Q000187:drug effects / Q000528:radiation effects; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D009010:Monte Carlo Method; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D019047:Phantoms, Imaging; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D011879:Radiotherapy Dosage
chemical_list: D020533:Angiogenesis Inhibitors; D011838:Radiation-Sensitizing Agents; D006046:Gold