Establishment of a Trimodality Analytical Platform for Tracing, Imaging and Quantification of Gold Nanoparticles in Animals by Radiotracer Techniques

This study aims to establish a Au-198-radiotracer technique for in vivo tracing, rapid quantification, and ex vivo visualization of PEGylated gold nanoparticles (GNPs) in animals, organs and tissue dissections. The advantages of GNPs lie in its superior optical property, biocompatibility and versatile conjugation chemistry, which are promising to develop diagnostic probes and drug delivery systems. Au-198 is used as a radiotracer because it simultaneously emits beta and gamma radiations with proper energy and half-life; therefore, Au-198 can be used for bioanalytical purposes. The Au-198-tagged radioactive gold nanoparticles (Au-198-GNPs) were prepared simply by irradiating the GNPs in a nuclear reactor through the 197Au(n,gamma)Au-198 reaction and subsequently the Au-198-GNPs were subjected to surface modification with polyethylene glycol to form PEGylated Au-198-GNPs. The Au-198-GNPs retained physicochemical properties that were the same as those of GNP before neutron irradiation. Pharmacokinetic and biodisposition studies were performed by intravenously injecting three types of Au-198-GNPs with or without PEGylation into mice; the gamma radiation in blood specimens and dissected organs was then measured. The Au-198-radiotracer technique enables rapid quantification freed from tedious sample preparation and shows more than 95% recovery of injected GNPs. Clinical gamma scintigraphy was proved feasible to explore spatial- and temporal-resolved biodisposition of Au-198-GNPs in living animals. Moreover, autoradiography, which recorded beta particles from Au-198, enabled visualizing the heterogeneous biodisposition of Au-198-GNPs in different microenvironments and tissues. In this study, the Au-198-radiotracer technique facilitated creating a trimodality analytical platform for tracing, quantifying and imaging GNPs in animals.