Low-Dose Prostate Cancer Brachytherapy with Radioactive Palladium-Gold Nanoparticles

Abstract

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 (¹⁰³ Pd:Pd@Au-PEG and ¹⁰³ Pd:Pd@¹⁹⁸ Au: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 ¹⁰³ Pd:Pd@Au-PEG NPs and ¹⁰³ Pd:Pd@¹⁹⁸ Au:Au-PEG NPs, respectively. Skin necrosis is observed with ¹⁹⁸ Au; therefore, Au NPs labeled with ¹⁰³ Pd only are a more advisable choice. Overall, this is the first study confirming the impact of ¹⁰³ Pd@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.

Keywords: alginate; intratumoral injections; low-dose brachytherapy; palladium-gold nanoparticles; prostate cancer; radioactive gold nanoparticles; radioactive palladium.