Low‐Dose Prostate Cancer Brachytherapy with Radioactive Palladium–Gold Nanoparticles

• Published in: Advanced healthcare materials 2017-02, Vol.6 (4), p.np-n/a
• Main Authors: Laprise‐Pelletier, Myriam, Lagueux, Jean, Côté, Marie‐France, LaGrange, Thomas, Fortin, Marc‐André
• Format: Article
• Language: English
• Subjects: alginate; Animals; Brachytherapy - methods; Cancer; Cell Line, Tumor; Gold; Gold - chemistry; Gold - pharmacology; Humans; Implantation; intratumoral injections; low‐dose brachytherapy; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Palladium - chemistry; Palladium - pharmacology; palladium–gold nanoparticles; Prostate; prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; radioactive gold nanoparticles; radioactive palladium; Seeds; Tumors; Xenograft Model Antitumor Assays
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201601120

Prostate cancer (PCa) is one of the leading causes of death among men. Low‐dose brachytherapy is an increasingly used treatment for PCa, which requires the implantation of tens of radioactive seeds. This treatment causes discomfort; these implants cannot be removed, and they generate image artifacts. In this study, the authors report on intratumoral injections of radioactive gold nanoparticles (Au NPs) as an alternative to seeds. The particles (103Pd:Pd@Au‐PEG and 103Pd:Pd@198Au:Au‐PEG; 10–14 nm Pd@Au core, 36–48 nm hydrodynamic diameter) are synthesized by a one‐pot process and characterized by electron microscopy. Administrated as low volume (2–4 µL) single doses (1.6–1.7 mCi), the particles are strongly retained in PCa xenograft tumors, impacting on their growth rate. After 4 weeks, a tumor volume inhibition of 56% and of 75%, compared to the controls, is observed for 103Pd:Pd@Au‐PEG NPs and 103Pd:Pd@198Au:Au‐PEG NPs, respectively. Skin necrosis is observed with 198Au; therefore, Au NPs labeled with 103Pd only are a more advisable choice. Overall, this is the first study confirming the impact of 103Pd@Au NPs on tumor growth. This new brachytherapy procedure could allow tunable doses of radioactivity, administered with smaller needles than with the current technologies, and leading to fewer image artifacts. Radioactive nanoparticles (103Pd:Pd@Au‐PEG and 103Pd:Pd@198Au:Au‐PEG) are developed as a new alternative to brachytherapy seed implants. Schematic representation of current millimeter‐size seed implantation (left) and proposed radioactive Pd@Au NPs (right) for the treatment of prostate cancer.