Radiosensitization of Prostate Cancers in Vitro and in Vivo to Erbium-filtered Orthovoltage X-rays Using Actively Targeted Gold Nanoparticles

Allison M. Khoo, Sang Hyun Cho, Francisco J. Reynoso, Maureen Aliru, Kathryn Aziz, Monica Bodd, Xi Yang, Md F. Ahmed, Selcuk Yasar, Nivedh Manohar, Jongmin Cho, Ramesh Tailor, Howard D. Thames, Sunil Krishnan

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Theoretical investigations suggest that gold nanoparticle (GNP)-mediated radiation dose enhancement and radiosensitization can be maximized when photons interact with gold, predominantly via photoelectric absorption. This makes ytterbium (Yb)-169, which emits photons with an average energy of 93 keV (just above the K-edge of gold), an ideal radioisotope for such purposes. This investigation tests the feasibility of tumor-specific prostate brachytherapy achievable with Yb-169 and actively targeted GNPs, using an external beam surrogate of Yb-169 created from an exotic filter material - erbium (Er) and a standard copper-filtered 250 kVp beam. The current in vitro study shows that treatment of prostate cancer cells with goserelin-conjugated gold nanorods (gGNRs) promotes gonadotropin releasing hormone receptor-mediated internalization and enhances radiosensitivity to both Er-filtered and standard 250 kVp beams, 14 and 10%, respectively. While the degree of GNP-mediated radiosensitization as seen from the in vitro study may be considered moderate, the current in vivo study shows that gGNR treatment plus Er-filtered x-ray irradiation is considerably more effective than radiation treatment alone (p < 0.0005), resulting in a striking reduction in tumor volume (50% smaller) 2 months following treatment. Overall, the current results provide strong evidence for the feasibility of tumor-specific prostate brachytherapy with Yb-169 and gGNRs.

Original languageEnglish
Article number18044
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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