Flow synthesis of intrinsically radiolabeled and renal-clearable ultrasmall [Au-198]Au nanoparticles in a PTFE microchannel

Synthesis of ultrasmall, citrate functionalized and intrinsically radiolabeled [Au-198]Au nanoparticles ([Au-198]Au NPs) below 5 nm diameter in a polytetrafluoroethylene (PTFE) microreactor is reported. The radioactive gold precursor along with trisodiumcitrate were premixed and infused into a PTFE microbore tube kept immersed inside a hot oil bath using a syringe pump. The synthesized [Au-198]Au NPs were mostly spherical in shape. Systematic studies were conducted to investigate effect of residence time, reaction temperature and citrate to gold ratio on the average particle size of the nanoparticles. The radioactive nanoparticles demonstrated excellent radiochemical stability under both in vitro and in vivo conditions. Biodistribution studies of the ultrasmall [Au-198]Au NPs in healthy Wistar rats showed fast clearance of the formulation (>85%ID at 24 h post-injection) predominantly through renal route, with its elimination half-life comparable to that of clinically used small molecule-based radiopharmaceuticals. Overall, this strategy of synthesis of ultrasmall intrinsically radiolabeled nanoparticles in a microreactor will potentially lay down the foundation for further development of renal clearable inorganic radionanomedicines with minimized toxicity for clinical translation.

Automated summary

A method for synthesizing ultrasmall, citrate-functionalized, and intrinsically radiolabeled [Au-198]Au nanoparticles in a polytetrafluoroethylene (PTFE) microreactor is reported. The synthesized nanoparticles showed excellent radiochemical stability and fast clearance through the renal route in biodistribution studies. This strategy has the potential to lay the foundation for the development of renal-clearable inorganic radionanomedicines with minimized toxicity for clinical translation.