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

A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225

“…In this perspective, radioactive nanoparticles could represent a promising alternative to current brachytherapy methods with outstanding results compared to conventional brachytherapy. A recent example of this approach is the work by Laprise-Pelletier et al, who report on a new brachytherapy procedure involving intratumoral injections of radioactive Au NPs as a form of brachytherapy for prostate cancer [5]. Herein, we propose a novel radiation nanomedicine that can be applied as unconventional brachytherapy in injectable form, after local intratumoral injection of gold nanoparticles labeled with an alpha (α-) emitter.…”

Gold Nanoparticles in Radiotherapy and Recent Progress in Nanobrachytherapy

“…The slight diffusion of GNPs from the immediate site of injection in the biological tissues represents a challenge for the integration of GNPs' aspects in a calculation dose planner. This migration phenomenon, which was confirmed in vivo, depends not only on the size of the GNPs, but also on the physicochemical characteristics of the particle surface . Because GNPs' migration cannot be measured on a case basis in patients and certainly not by biopsies, this behavior must be carefully assessed in tumor models featuring similar density, vascularization, and biochemical signatures compared with the target type of tumors in humans.…”

“…C) Biocompatible reduction route used to synthesize core–shell GNPs based on 103 Pd and 198 Au isotopes ( 103 Pd:Pd@Au‐PEG, 103 Pd:Pd@ 198 Au:Au–PEG). Adapted with permission . Copyright 2017, Wiley‐VCH.…”

“…Spleen uptake was also lower for targeted Au–T NPs (1.80 %ID g −1 ) versus (2.68 %ID g −1 ) for nontargeted Au‐NT. Co‐injection of the nanoparticles with a biocompatible polymer that sequestrate them in the tumors is also a strategy being studied . At this moment in the development of radioactive and radiolabeled GNPs, comprehensive biodistribution studies are needed to reveal and to control the excretion routes of GNPs.…”

Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer

“…So far though, this technique has only been used occasionally in PCa and BC NP applications. Since EM is not considered to be an imaging technique possible to use in theranostic contexts, its value lies instead in in vitro and ex vivo analyses, as mentioned above, or during the production process of the NPs in order to be able to characterize them properly [401,402,403,404,405,406,407,408]. …”