Radioactive gold nanoparticles could track drug distribution in the body

Gold nanoparticles are promising vehicles for targeted delivery of cancer drugs, offering biocompatibility plus a tendency to accumulate in tumours. To fully exploit their potential, it’s essential to be able to track the movement of these nanoparticles in the body. To date, however, methods for directly visualizing their pharmacokinetics have not yet been established. Aiming to address this shortfall, researchers in Japan are using neutron-activated gold radioisotopes to image nanoparticle distribution in vivo.
The team, headed up by Nanase Koshikawa and Jun Kataoka from Waseda University, are investigating the use of radioactive gold nanoparticles based on 198Au, which they create by irradiating stable gold (197Au) with low-energy neutrons. The radioisotope 198Au has a half-life of 2.7 days and emits 412 keV gamma rays, enabling a technique known as activation imaging.
“Our motivation was to visualize gold nanoparticles without labelling them with tracers,” explains Koshikawa. “Radioactivation allows gold nanoparticles themselves to become detectable from outside the body. We used neutron activation because it does not change the atomic number, ensuring the chemical properties of gold nanoparticles remain unchanged.”
In vivo studies
The researchers – also from Osaka University and Kyoto University – synthesized 198Au-based nanoparticles and injected them into tumours in four mice. They used a hybrid Compton camera (HCC) to detect the emitted 412 keV gamma rays and determine the in vivo nanoparticle distribution, on the day of injection and three and five days later.
The HCC, which incorporates two pixelated scintillators, a scatterer with a central pinhole, and an absorber, can detect radiation with energies from tens of keV to nearly 1 MeV. For X-rays and low-energy gamma rays, the scatterer enables pinhole-mode imaging. For gamma rays over 200 keV, the device functions as a Compton camera.
The researchers reconstructed the 412 keV gamma signals into images, using an energy window of 412±30 keV. With the HCC located 5 cm from the animals’ abdomens, the spatial resolution was 7.9 mm, roughly comparable to the tumour size on the day of injection (7.7 x 11 mm).

Overlaying the images onto photographs of the mice revealed that the nanoparticles accumulated in both the tumour and liver. In mice 1 and 2, high pixel values were observed primarily in the tumour, while mice 3 and 4 also had high pixel values in the liver region.
After imaging, the mice were euthanized and the team used a gamma counter to measure the radioactivity of each organ. The measured activity concentrations were consistent with the imaging results: mice 1 and 2 had higher nanoparticle concentrations in the tumour than the liver, and mice 3 and 4 had higher concentrations in the liver.
Tracking drug distribution
Next, Koshikawa and colleagues used the 198Au nanoparticles to label astatine-211 (211At), a promising alpha-emitting drug. They note that although 211At emits 79 keV X-rays, allowing in vivo visualization, its short half-life of just 7.2 h precludes its use for long-term tracking of drug pharmacokinetics.
The researchers injected the 211At-labelled nanoparticles into three tumour-bearing mice and used the HCC to simultaneously image 211At and 198Au, on the day of injection and one or two days later. Comparing energy spectra recorded just after injection with those two days later showed that the 211At peak at 79 keV significantly decreased in height owing to its decay, while the 412 keV 198Au peak maintained its height.
The team reconstructed images using energy windows of 79±10 and 412±30 keV, for pinhole- and Compton-mode reconstruction, respectively. In these experiments, the HCC was placed 10 cm from the mouse, giving a spatial resolution of 16 mm – larger than the initial tumour size and insufficient to clearly distinguish tumours from small organs. Nevertheless, the researchers point out that the rough distribution of the drug was still observable.
On the day of injection, the drug distribution could be visualized using both the 211At and 198Au signals. Two days later, imaging using 211At was no longer possible. In contrast, the distribution of the drug could still be observed via the 412 keV gamma rays.
With further development, the technique may prove suitable for future clinical use. “We assume that the gamma ray exposure dose would be comparable to that of clinical imaging techniques using X-rays or gamma rays, such as SPECT and PET, and that activation imaging is not harmful to humans,” Koshikawa says.
Activation imaging could also be applied to more than just gold nanoparticles. “We are currently working on radioactivation of platinum-based anticancer drugs to enable their visualization from outside the body,” Koshikawa tells Physics World. “Additionally, we are developing new detectors to image radioactive drugs with higher spatial resolution.”
The findings are reported in Applied Physics Letters.
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