Fabrication of {¹⁹⁸Au⁰} radioactive composite nanodevices and their use for nanobrachytherapy

We describe the simple fabrication of poly({¹⁹⁸Au}) radioactive gold-dendrimer composite nanodevices in distinct sizes (diameter between 10 nm and 29 nm) for targeted radiopharmaceutical dose delivery to tumors in vivo. Irradiation of aqueous solutions of ¹⁹⁷Au containing poly(amidoamine) dendrimer tetrachloroaurate salts or {¹⁹⁷Au⁰} gold-dendrimer nanocomposites in a nuclear reactor resulted in the formation of positively charged and soluble poly{¹⁹⁸Au⁰} radioactive composite nanodevices (CNDs). A mouse melanoma tumor model was used to test whether the poly{¹⁹⁸Au⁰} CNDs can deliver a therapeutic dose. A single intratumoral injection of poly{¹⁹⁸Au⁰}_d=22nm CNDs in phosphate-buffered saline delivering a dose of 74 μCi resulted after 8 days in a statistically significant 45% reduction in tumor volume, when compared with untreated groups and those injected with the "cold" nanodevice. No clinical toxicity was observed during the experiments. This study provides the first proof of principle that radioactive CNDs can deliver therapeutic doses to tumors.