日本研究人员开发了一种创新的激活成像技术，利用中子活化金纳米粒子，实现了在不使用外部示踪剂的情况下，实时可视化体内金纳米粒子的分布。该技术基于198Au放射性同位素，通过检测其释放的412 keV伽马射线，能够追踪纳米粒子在肿瘤和肝脏中的积累情况，为靶向药物递送的研究提供了新的视角。研究还成功将该技术应用于标记阿斯他汀-211（211At）药物，实现了对药物药代动力学的长期追踪，为未来临床应用提供了可能性。

🔬研究团队通过中子辐照稳定的金(197Au)制备了放射性金纳米粒子198Au，该同位素半衰期为2.7天，发射412 keV伽马射线，从而实现激活成像。

📍研究人员将198Au纳米粒子注入小鼠肿瘤中，使用混合康普顿相机(HCC)检测伽马射线，确定体内纳米粒子的分布。结果显示，纳米粒子主要积聚在肿瘤和肝脏中，与后续的器官放射性测量结果一致。

💊该技术被用于标记阿斯他汀-211(211At)药物，实现了对药物分布的追踪。通过比较注射当天和两天后的能量谱，研究人员发现211At峰值下降，而198Au峰值保持不变，表明该技术可用于长期追踪药物药代动力学。

💡该技术在未来具有潜在的临床应用价值，研究人员认为伽马射线暴露剂量与临床成像技术（如SPECT和PET）相当，对人体无害。研究团队还在开发基于铂的抗癌药物的放射活化技术，并研制具有更高空间分辨率的新型探测器。

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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