Synthesis of radioactive gold nanoparticles for brachytherapy treatments using plasma electrochemistry

Abstract

Event Abstract Back to Event Synthesis of radioactive gold nanoparticles for brachytherapy treatments using plasma electrochemistry Mathieu Bouchard1, 2, 3, Myriam Laprise-Pelletier1, 2, 3, Stéphane Turgeon2 and Marc-André Fortin1, 2, 3 1 Université Laval, Génie des mines, de la métallurgie et des matériaux, Canada 2 Université Laval, Centre hospitalier universitaire de Québec, Canada 3 Université Laval, Centre de recherche sur les matériaux avancés (CERMA), Canada Gold nanoparticles (Au NPs) are increasingly considered for use as biocompatible radioactive sources (198Au) for prostate brachytherapy procedures[1],[2]. The range of the 198Au β-particle (0.96 MeV, ~ 11 mm in soft tissue, ~ 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland, and short enough to minimize the dose to healthy peripheral tissues. The integration of 198Au NPs into brachytherapy procedures requires the development of more efficient, safer, and more compact Au NP synthesis methods. Indeed, because of their relatively short half-life (2.7 days), 198Au NPs should ideally be synthesized on-site (directly in hospitals) and upon request. However, the current NP colloidal synthesis methods invariably rely on the expertise of skilled chemists, and require several manipulation steps (ligand and solvent exchange, purification procedures), which represent critical radioprotection challenges. Here we report on a novel bench-top technology based on plasma-liquid electrochemistry that facilitates the automated production of 198Au NPs directly in water. Plasma consists of an ionized gas: it contains electrons, positive ions, UV photons and excited chemical species. The reactor we developed allowed the generation of large-area atmospheric pressure argon plasma at the surface of a liquid containing 1 mM of gold salts (Fig.1)[3]. Radioactive 198Au salts were added with an initial activity of 500 µCi. We used dextran, a biocompatible polymer widely used in vascular injection media, to stabilise the NPs with specific sizes and shapes. A UV-vis spectrometer allowed the in situ monitoring of the NP solution throughout the synthesis (Fig.2: plasmon peak, usually between 530 and 570 nm depending on NP sizes), which is necessary for quality control. The plasma treatment was followed by a rapid purification procedure involving centrifugation and filtration to separate the NPs according to their size. The highly reactive species in the plasma allowed the reduction of gold ions into very stable NPs at the plasma-liquid interface. Within 30 minutes, a 20 mL solution of Au NPs was produced. Two different size distributions were obtained and efficiently separated, with mean diameters of 26 and 44 nm (Fig.3). SPECT imaging showed the internalization of 198Au atoms into the NP matrices. A "ripening" period of 16 hours after plasma treatment led to the reduction of the remaining gold salts through seed-mediated growth, up to a reduction yield over 99.9%. The size distribution was also shifted toward more uniform and larger diameters (> 50 nm). Overall, plasma electrochemistry could enable the rapid, efficient and on-site production of quality-controlled 198Au NPs for a next generation of brachytherapy procedures. Further work is required to understand the exact electrochemical mechanisms responsible for the synthesis, which will surely open the way to new applications of atmospheric plasma reactors in the biomaterials field. Julie-Christine Lévesque