Localized Dose Enhancement to Tumor Blood Vessel Endothelial Cells via Megavoltage X-rays and Targeted Gold Nanoparticles: New Potential for External Beam Radiotherapy

Journal Article · Thu Sep 01 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.10.022· OSTI ID:21587711

Ngwa, Wilfred; Makrigiorgos, G Mike ^[1]

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1. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (United States)

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.

• OSTI ID: 21587711
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 81, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2010.10.022; PII: S0360-3016(10)03443-7; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ANGIOGENESIS
BLOOD VESSELS
ENDOTHELIUM
GOLD
HAZARDS
IRRADIATION
KEV RANGE 10-100
MICRODOSIMETRY
MICROSTRUCTURE
MONTE CARLO METHOD
NANOSTRUCTURES
NEOPLASMS
RADIATION DOSES
RADIATION INJURIES
RADIOTHERAPY
X RADIATION
X-RAY SPECTRA
ANIMAL TISSUES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
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CARDIOVASCULAR SYSTEM
DISEASES
DOSES
DOSIMETRY
ELECTROMAGNETIC RADIATION
ELEMENTS
ENERGY RANGE
INJURIES
IONIZING RADIATIONS
KEV RANGE
MEDICINE
METALS
NUCLEAR MEDICINE
ORGANS
RADIATION EFFECTS
RADIATIONS
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