Activation imaging of gold nanoparticles for versatile drug visualization: An in vivo demonstration

Abstract

Gold nanoparticles (AuNPs) have recently attracted considerable attention as promising drug carriers. In vivo imaging of AuNPs is required to investigate their pharmacokinetics. However, a direct and highly sensitive method has not yet been established. Therefore, we proposed the activation imaging of AuNPs that radioactivates AuNPs and non-invasively visualizes them using the emitted gamma rays. When the stable isotope of gold, ¹⁹⁷Au, is irradiated with low-energy neutrons, it changes to radioactive ¹⁹⁸Au, which predominantly emits 412-keV gamma rays. In this study, we synthesized [¹⁹⁸Au]AuNPs through neutron irradiation and intratumorally injected them into tumor-bearing mice. In vivo imaging was performed using wideband x rays and gamma rays imager, and the distribution of [¹⁹⁸Au]AuNPs in the body of mice was observed. Furthermore, we labeled the alpha-emitting therapeutic drug ²¹¹At with [¹⁹⁸Au]AuNPs. Although ²¹¹At itself can be visualized using its 79-keV x rays, the long-term tracking of ²¹¹At-labeled AuNPs has been challenging due to its relatively short half-life of 7.2 h. The activation of AuNPs enables the long-term tracking of ²¹¹At-labeled AuNPs owing to the 2.7-day half-life of ¹⁹⁸Au. ²¹¹At-labeled [¹⁹⁸Au]AuNPs were injected intravenously into mice and visualized using a wideband x rays and gamma rays imager. Simultaneous imaging of ²¹¹At and ¹⁹⁸Au was performed on the day of injection and 2 days after injection. Although ²¹¹At could no longer be imaged 2 days after injection, the distribution of the drug was visualized using gamma rays from ¹⁹⁸Au.