Journal of Medical and Biological Engineering

, Volume 35, Issue 5, pp 634–642 | Cite as

Effect of External Targeted Radiotherapy on Dosimetry Due to Rapid Clearance of Gold Nanoparticles

  • Shu-Ju Tu
  • Pei-Ying Yang
  • Ching-Jung Lo
Original Article


Progress in the application of gold nanoparticles (GNPs) in the biomedical research of small animals has substantially advanced in recent years. Studies suggest a high potential of applying nanoparticle technology to the targeted drug delivery and sensitization system for external beam radiotherapy. Therefore, a scenario of integrated cancer therapy is highly expected, in which patients are treated with administration of GNP media and external beam radiotherapy simultaneously. However, a possible problem is that GNPs may be rapidly transported through the circulatory system to the kidneys, accumulating in the bladder. As a consequence, dosimetric variations could occur as GNP media are absent in the treatment planning, but present in the bladder at a high density during treatment delivery. This study investigates the effect of the rapid clearance of GNPs on dosimetric variations and biological consequences. A prostate phantom and five clinical cases are included. Intensity-modulated radiation therapy (IMRT) and RapidArc are used as the treatment techniques. Dose-volume histograms show that the amounts of dose delivered to the prostate planning target volume (PTV), bladder, and rectum decrease. Linear correlations between the concentration of GNP media in the bladder and the corresponding percentage changes of mean dose at the PTV are formulated. For biological consequences, high-dose regions in the mucosal areas of the bladder and rectum are identified. To manage a dosimetric variation of less than 3 % for the prostate PTV, the phantom study results suggest an upper threshold of 97.48 mg-Au/mL with IMRT and 168.22 mg-Au/mL with RapidArc, whereas the clinical study suggests 131.58 mg-Au/mL with RapidArc.


Gold nanoparticles Clearance effect Targeted radiotherapy Intensity-modulated radiation therapy Volumetric modulated arc therapy RapidArc 



This work was supported by research grants from the Ministry of Science and Technology in Taiwan and the Research and Development Department at Chang Gung Memorial Hospital of Taiwan (CIRPD1C0043 and CMRPD1C0672).

Compliance with Ethical Standards

Conflict of interests

The authors declare that there is no conflict of interests regarding the publication of this article.


  1. 1.
    Boisselier, E., & Astruc, D. (2009). Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies and toxicity. Chemical Society Reviews, 38, 1759–1782.CrossRefGoogle Scholar
  2. 2.
    Cheng, Z., Al Zaki, A., Hui, J. Z., Muzykantov, V. R., & Tsourkas, A. (2012). Multifunctional nanoparticles: Cost versus benefit of adding targeting and imaging capabilities”. Science, 338, 903–910.CrossRefGoogle Scholar
  3. 3.
    Jain, S., Hirst, D. G., & O’Sullivan, J. M. (2012). Gold nanoparticles as novel agents for cancer therapy. The British Journal of Radiolgy, 85, 101–113.CrossRefGoogle Scholar
  4. 4.
    Mesbahi, A. (2010). A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer. Reports of Practical Oncology Radiotherapy, 15, 176–180.CrossRefGoogle Scholar
  5. 5.
    Peng, C., Zheng, L., Chen, Q., Shen, M., Guo, R., Wang, H., et al. (2012). PEGylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography. Biomaterials, 33, 1107–1119.CrossRefGoogle Scholar
  6. 6.
    Amato, E., Italiano, A., & Pergolizzi, S. (2013). Gold nanoparticles as a sensitising agent in external beam radiotherapy and brachytherapy: A feasibility study through Monte Carlo simulation. International Journal of Nanotechnology, 10, 1045–1054.CrossRefGoogle Scholar
  7. 7.
    Berbeco, R. I., Ngwa, W., & Makrigiorgos, G. M. (2011). Localized dose enhancement to tumor blood vessel endothelial cells via megavoltage X-rays and targeted gold nanoparticles: New potential for external beam radiotherapy. International Journal of Radiation Oncology Biology Physics, 81, 270–276.CrossRefGoogle Scholar
  8. 8.
    Krause, M., Zips, D., Thames, H. D., Kummermehr, J., & Baumann, M. (2006). Preclinical evaluation of molecular-targeted anticancer agents for radiotherapy. Radiotherapy and Oncology, 80, 112–122.CrossRefGoogle Scholar
  9. 9.
    Tsiamas, P., Liu, B., Cifter, F., Ngwa, W. F., Berbeco, R. I., Kappas, C., et al. (2013). Impact of beam quality on megavoltage radiotherapy treatment techniques utilizing gold nanoparticles for dose enhancement. Physics in Medicine & Biology, 58, 451–464.CrossRefGoogle Scholar
  10. 10.
    Tu, S. J., Yang, P. Y., Hong, J. H., & Lo, C. J. (2013). Quantitative dosimetric assessment for effect of gold nanoparticles as contrast media on radiotherapy planning. Radiation Physics and Chemistry, 88, 14–20.CrossRefGoogle Scholar
  11. 11.
    Arias, J. L. (2011). Advanced methodologies to formulate nanotheragnostic agents for combined drug delivery and imaging. Expert Opinion on Drug Delivery, 8, 1589–1608.CrossRefGoogle Scholar
  12. 12.
    Ceresa, C., Bravin, A., Cavaletti, G., Pellei, M., & Santini, C. (2014). The combined therapeutical effect of metal-based drugs and radiation therapy: The present status of research. Current Medicinal Chemistry, 21, 2237–2265.CrossRefGoogle Scholar
  13. 13.
    Patel, N. R., Pattni, B. S., Abouzeid, A. H., & Torchilin, V. P. (2013). Nanopreparations to overcome multidrug resistance in cancer. Advanced Drug Delivery Reviews, 65, 1748–1762.CrossRefGoogle Scholar
  14. 14.
    Khadem-Abolfazli, M., Mahdavi, M., Mahdavi, S. R. M., & Ataei, G. (2013). Dose enhancement effect of gold nanoparticles on MAGICA polymer gel in mega voltage radiation therapy. International Journal of Radiation Research, 11, 55–61.Google Scholar
  15. 15.
    Pakravan, D., Ghorbani, M., & Momennezhad, M. (2013). Tumor dose enhancement by gold nanoparticles in a 6 mv photon beam: A monte carlo study on the size effect of nanoparticles. Nukleonika, 58, 275–280.Google Scholar
  16. 16.
    Robar, J. L., Riccio, S. A., & Martin, M. A. (2002). Tumour dose enhancement using modified megavoltage photon beams and contrast media. Physics in Medicine & Biology, 47, 2433–2449.CrossRefGoogle Scholar
  17. 17.
    Hainfeld, J. F., Smilowitz, H. M., O’Connor, M. J., Dilmanian, F. A., & Slatkin, D. N. (2013). Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine, 8, 1601–1609.CrossRefGoogle Scholar
  18. 18.
    Jeremic, B., Aguerri, A. R., & Filipovic, N. (2013). Radiosensitization by gold nanoparticles. Clinical and Translational Oncology, 15, 593–601.CrossRefGoogle Scholar
  19. 19.
    McMahon, S. J., Mendenhall, M. H., Jain, S., & Currell, F. (2008). Radiotherapy in the presence of contrast agents: A general figure of merit and its application to gold nanoparticles. Physics in Medicine & Biology, 53, 5635–5651.CrossRefGoogle Scholar
  20. 20.
    Mousavie Anijdan, S. H., Shirazi, A., Mahdavi, S. R., Ezzati, A., Mofid, B., Khoei, S., & Zarrinfard, M. A. (2012). Megavoltage dose enhancement of gold nanoparticles for different geometric set-ups: Measurements and monte carlo simulation. International Journal of Radiation Research, 10, 183–186.Google Scholar
  21. 21.
    Ezzell, G. A., Burmeister, J. W., Dogan, N., Losasso, T. J., Mechalakos, J. G., Mihailidis, D., et al. (2009). IMRT commissioning: Multiple institution planning and dosimetry comparisons, a report from AAPM Task Group 119. Medical Physics, 36, 5359–5373.CrossRefGoogle Scholar
  22. 22.
    Hainfeld, J. F., Dilmanian, F. A., Zhong, Z., Slatkin, D. N., Kalef-Ezra, J. A., & Smilowitz, H. M. (2010). Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma. Physics in Medicine & Biology, 55, 3045.CrossRefGoogle Scholar
  23. 23.
    Hainfeld, J. F., Slatkin, D. N., Focella, T. M., & Smilowitz, H. M. (2006). Gold nanoparticles: A new X-ray contrast agent. The British Journal of Radiology, 79, 248–253.CrossRefGoogle Scholar
  24. 24.
    Ost, P., Speleers, B., De Meerleer, G., De Neve, W., Fonteyne, V., Villeirs, G., & De Gersem, W. (2011). Volumetric arc therapy and intensity-modulated radiotherapy for primary prostate radiotherapy with simultaneous integrated boost to intraprostatic lesion with 6 and 18 MV: A planning comparison study. International Journal of Radiation Oncology Biology Physics, 79, 920–926.CrossRefGoogle Scholar
  25. 25.
    Otto, K. (2008). Volumetric modulated arc therapy: IMRT in a single gantry arc. Medical Physics, 35, 310–317.CrossRefGoogle Scholar
  26. 26.
    Yao, C. H., Hsu, W. T., Lee, J. J., Hsu, S. M., Ma, P. Y. L., Hsieh, B. T., & Chang, Y. J. (2014). A characteristic study on NIPAM gel dosimetry using optical-CT scanner. Journal of Medical and Biological Engineering, 34, 327–332.CrossRefGoogle Scholar
  27. 27.
    Baumann, M., & Petersen, C. (2005). TCP and NTCP: A basic introduction. Rays International Journal of Radiology and Radiation Science, 30, 99–104.Google Scholar
  28. 28.
    Cabrera, A. R., & Lee, W. R. (2013). Hypofractionation for clinically localized prostate cancer. Seminars in Radiation Oncology, 23, 191–197.CrossRefGoogle Scholar
  29. 29.
    Miles, E. F., & Robert Lee, W. (2008). Hypofractionation for prostate cancer: A critical review. Seminars in Radiation Oncology, 18, 41–47.CrossRefGoogle Scholar
  30. 30.
    Vavassis, P., Nguyen, D. H., Bahary, J. P., & Yassa, M. (2012). Hypofractionated radiotherapy in prostate cancer. Expert Review of Anticancer Therapy, 12, 965–972.CrossRefGoogle Scholar
  31. 31.
    Dawson, L. A., & Sharpe, M. B. (2006). Image-guided radiotherapy: Rationale, benefits, and limitations. The Lancet Oncology, 7, 848–858.CrossRefGoogle Scholar
  32. 32.
    Jaffray, D. A. (2012). Image-guided radiotherapy: From current concept to future perspectives. Nature Reviews Clinical Oncology, 9, 688–699.CrossRefGoogle Scholar

Copyright information

© Taiwanese Society of Biomedical Engineering 2015

Authors and Affiliations

  1. 1.Department of Medical Imaging and Radiological Sciences College of MedicineChang Gung UniversityTao-YuanTaiwan
  2. 2.Department of Radiation OncologyChang Gung Memorial HospitalTao-YuanTaiwan

Personalised recommendations