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Medical Physics / Volume 39 / Issue 1 / RADIATION THERAPY PHYSICS

Med. Phys. 39, 392 (2012); http://dx.doi.org/10.1118/1.3671905 (7 pages)

Gold nanoparticle-aided brachytherapy with vascular dose painting: Estimation of dose enhancement to the tumor endothelial cell nucleus

Wilfred Ngwa, G. Mike Makrigiorgos, and Ross I. Berbeco

Department of Radiation Oncology, Division of Medical Physics and Biophysics, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115

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(Received 29 September 2011; accepted 1 December 2011; revised 1 December 2011; published online 22 December 2011)

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Purpose: Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy.
Methods: A tumor vascular endothelial cell (EC) is modeled as a slab of 2 μm (thickness) × 10 μm (length) × 10 μm (width). The EC contains a nucleus of 5 μm diameter and thickness of 0.5–1 μm, corresponding to nucleus size 5%–10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated.
Results: For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6–73, 4.8–58.3, 4.7–56.6, and 3.2–25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9–79.2, 5.1–63.2, 5.0–61.5, and 3.3–28.3, respectively.
Conclusions: The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting extensive tumor cell death.

© 2012 American Association of Physicists in Medicine

Article Outline

  1. INTRODUCTION
  2. METHODS
  3. RESULTS
  4. DISCUSSION
  5. CONCLUSION
Digital Object Identifier
http://dx.doi.org/10.1118/1.3671905

KEYWORDS and PACS

Keywords

brachytherapy, cellular effects of radiation, dosimetry, nanobiotechnology, nanoparticles, tumours, brachytherapy, gold nanoparticles, vascular disrupting agents, dose enhancement

PACS

  • 87.53.Jw

    Therapeutic applications, including brachytherapy

  • 87.85.Rs

    Nanotechnologies-applications

  • 87.53.Bn

    Dosimetry/exposure assessment

PUBLICATION DATA

ISSN

0094-2405 (print)  

Publisher

$abstract.society.value is a Member of CrossRef American Association of Physicists in Medicine

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Figures (click on thumbnails to view enlargements)

FIG.1
Simplified slab model (2 μm (thickness) × 10 μm (length) × 10 μm (width) of an endothelial cell between the lumen and the tumor cells. The gold nanoparticles are attached to the lumen side of the endothelial cell. The range of electrons is shown as a “sphere of interaction” with the nanoparticle at the center. Only the dose deposited by electrons within the 1 μm thick slab section enclosing the nucleus within the circle of interaction is used to calculate the dose enhancement to the nucleus. (Diagrams not to scale.)

FIG.1 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.2
nDEF as a function of local concentration for: (a) nucleus size 5% of the cellular volume and (b) nucleus size 10% of cellular volume.

FIG.2 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.3
nDEF as a function of location for: (a) nucleus size 5% of the cellular volume and (b) nucleus size 10% of cellular volume. Location zero is at the end of the endothelial cell proximal to the lumen.

FIG.3 Download High Resolution Image (.zip file) | Export Figure to PowerPoint

FIG.4
nDEF at concentration of 7 mg/g as a function of location for nucleus size 5% of the cellular volume due to: (a) photoelectrons and (b) Auger electrons.

FIG.4 Download High Resolution Image (.zip file) | Export Figure to PowerPoint



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