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

• Published in: International journal of radiation oncology, biology, physics Vol. 81; no. 1; pp. 270 - 276
• Main Authors: Berbeco, Ross I., Ph.D, Ngwa, Wilfred, Ph.D, Makrigiorgos, G. Mike, Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2011; Elsevier
• Subjects: Algorithms; ANGIOGENESIS; ANIMAL TISSUES; Anti-angiogenesis; Biological and medical sciences; BIOLOGICAL EFFECTS; BIOLOGICAL RADIATION EFFECTS; BLOOD VESSELS; BODY; CALCULATION METHODS; CARDIOVASCULAR SYSTEM; DISEASES; DOSES; DOSIMETRY; ELECTROMAGNETIC RADIATION; ELEMENTS; Endothelial Cells - radiation effects; ENDOTHELIUM; Endothelium, Vascular - cytology; ENERGY RANGE; GOLD; Gold - therapeutic use; HAZARDS; Hematology, Oncology and Palliative Medicine; INJURIES; IONIZING RADIATIONS; IRRADIATION; KEV RANGE; KEV RANGE 10-100; Medical sciences; MEDICINE; Metal Nanoparticles - therapeutic use; METALS; Microcirculation - radiation effects; MICRODOSIMETRY; MICROSTRUCTURE; MONTE CARLO METHOD; Nanoparticles; NANOSTRUCTURES; NEOPLASMS; Neoplasms - blood supply; Neoplasms - radiotherapy; NUCLEAR MEDICINE; ORGANS; Particle Accelerators; Photons - therapeutic use; RADIATION DOSES; RADIATION EFFECTS; RADIATION INJURIES; Radiation therapy and radiosensitizing agent; RADIATIONS; RADIOLOGY; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy - methods; Radiotherapy Dosage; SBRT; SPECTRA; THERAPY; TRANSITION ELEMENTS; Treatment with physical agents; Treatment. General aspects; Tumors; X RADIATION; X-RAY SPECTRA; Nanoparticles; SBRT; Anti-angiogenesis; Gold; Endothelial cell; Nanoparticle; Radiotherapy; Electrontherapy; Angiogenesis; Radiation dose; Treatment; Blood vessel; Radiation effect; Tumor; Circulatory system; Dosimetry
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2010.10.022

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.