Ross I Berbeco1, Wilfred Ngwa, G Mike Makrigiorgos. 1. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA. rberbeco@partners.org
Abstract
PURPOSE: Tumor endothelial cell damage during radiation therapy may contribute significantly to tumor eradication and treatment efficacy. Gold nanoparticles (AuNPs) delivered preferentially to the walls of tumor blood vessels produce low-energy, short-range photoelectrons during external beam radiotherapy, boosting dose to the tumor microvasculature. In this study dosimetry at the single-cell level is used to estimate the anticipated AuNP-mediated dose enhancement to tumor endothelial cells during 6-MV X-ray irradiation. METHODS AND MATERIALS: Endothelial cells are modeled as thin slabs with 100-nm-diameter AuNPs attached within the blood vessel. The number of photoelectrons emitted per AuNP per gray of X-rays is computed at multiple points along the external beam central axis by use of a Monte Carlo-generated energy fluence spectrum. The energy deposited from AuNP emissions to the endothelium is calculated based on an analytic method incorporating the energy-loss formula of Cole. The endothelial dose enhancement factor (EDEF) is the ratio of the overall (externally plus internally generated) dose to endothelial cells in the presence of AuNPs to the dose without AuNPs (from the external beam only). RESULTS: At 20-cm depth, the EDEF is 1.7 (70% dose increase) for an intravascular AuNP concentration of 30 mg/g. Most of this dose enhancement arises from the low-energy (approximately 100 keV) portion of the linear accelerator X-ray spectrum. Furthermore, for AuNP concentrations ranging from 7 to 140 mg/g, EDEF values of 1.2 to 4.4 (20-340% dose increase) are calculated. CONCLUSIONS: In contrast to calculations assuming that AuNPs distributed homogeneously throughout the target volume (macrodosimetry), our cellular microdosimetry calculations predict a major dose enhancement to tumor microvasculature from conventional linear accelerator X-rays. This effect may enable the delivery of ablative therapeutic doses to these sensitive microstructures while maintaining established dose constraints for the organs at risk.
PURPOSE:Tumor endothelial cell damage during radiation therapy may contribute significantly to tumor eradication and treatment efficacy. Gold nanoparticles (AuNPs) delivered preferentially to the walls of tumor blood vessels produce low-energy, short-range photoelectrons during external beam radiotherapy, boosting dose to the tumor microvasculature. In this study dosimetry at the single-cell level is used to estimate the anticipated AuNP-mediated dose enhancement to tumor endothelial cells during 6-MV X-ray irradiation. METHODS AND MATERIALS: Endothelial cells are modeled as thin slabs with 100-nm-diameter AuNPs attached within the blood vessel. The number of photoelectrons emitted per AuNP per gray of X-rays is computed at multiple points along the external beam central axis by use of a Monte Carlo-generated energy fluence spectrum. The energy deposited from AuNP emissions to the endothelium is calculated based on an analytic method incorporating the energy-loss formula of Cole. The endothelial dose enhancement factor (EDEF) is the ratio of the overall (externally plus internally generated) dose to endothelial cells in the presence of AuNPs to the dose without AuNPs (from the external beam only). RESULTS: At 20-cm depth, the EDEF is 1.7 (70% dose increase) for an intravascular AuNP concentration of 30 mg/g. Most of this dose enhancement arises from the low-energy (approximately 100 keV) portion of the linear accelerator X-ray spectrum. Furthermore, for AuNP concentrations ranging from 7 to 140 mg/g, EDEF values of 1.2 to 4.4 (20-340% dose increase) are calculated. CONCLUSIONS: In contrast to calculations assuming that AuNPs distributed homogeneously throughout the target volume (macrodosimetry), our cellular microdosimetry calculations predict a major dose enhancement to tumor microvasculature from conventional linear accelerator X-rays. This effect may enable the delivery of ablative therapeutic doses to these sensitive microstructures while maintaining established dose constraints for the organs at risk.
Authors: Ross I Berbeco; Alexandre Detappe; Panogiotis Tsiamas; David Parsons; Mammo Yewondwossen; James Robar Journal: Med Phys Date: 2016-01 Impact factor: 4.071
Authors: Ross I Berbeco; Houari Korideck; Wilfred Ngwa; Rajiv Kumar; Janki Patel; Srinivas Sridhar; Sarah Johnson; Brendan D Price; Alec Kimmelman; G Mike Makrigiorgos Journal: Radiat Res Date: 2012-11-13 Impact factor: 2.841
Authors: Yucel Altundal; Gizem Cifter; Alexandre Detappe; Erno Sajo; Panagiotis Tsiamas; Piotr Zygmanski; Ross Berbeco; Robert A Cormack; Mike Makrigiorgos; Wilfred Ngwa Journal: Phys Med Date: 2014-12-06 Impact factor: 2.685
Authors: D Brivio; P Zygmanski; M Arnoldussen; J Hanlon; E Chell; E Sajo; G M Makrigiorgos; W Ngwa Journal: Phys Med Biol Date: 2015-11-18 Impact factor: 3.609