Gold nanoparticle-aided brachytherapy with vascular dose painting: estimation of dose enhancement to the tumor endothelial cell nucleus.
OBJECTIVE
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.
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, USA. wngwa@lroc.harvard.edu
Wilfred
W
Ngwa
G Mike
GM
Makrigiorgos
Ross I
RI
Berbeco
D000818:Animals; D001918:Brachytherapy / Q000379:methods*; D002467:Cell Nucleus / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D003198:Computer Simulation; D042783:Endothelial Cells / Q000528:radiation effects*; D006046:Gold / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D011879:Radiotherapy Dosage
D006046:Gold