First Validation of Novel PRI Technology: Existing PET Tracers Can Image Tissue Microenvironment

On August 6, 2026, a joint research team from the Graduate School of Engineering at the University of Tokyo and the University of York in the UK announced that they have established a novel geometric imaging principle utilizing positron three-photon decay and successfully validated Positronium Ratio Imaging (PRI) technology for the first time. This method can be used in conjunction with existing clinical PET tracers and is expected to provide a new means of observing tissue microenvironments in nuclear medicine imaging.

Conceptual diagram of next-generation nuclear medicine imaging utilizing positron-3-photon decay

Current clinical PET scans primarily rely on the positron two-photon annihilation process to visualize the distribution and accumulation of tracers in the body, but they provide limited information on microenvironmental factors such as tissue hypoxia that are associated with disease malignancy. Previous research on positronium average lifetime imaging typically required the development of specialized radiopharmaceuticals, which posed a significant limitation for practical applications.

Schematic diagram of three-photon imaging principle

Imaging results when water and porous material (XAD-4) are mixed with 18F-FDG.

(a) Conventional two-photon PET image, (b) three-photon image, (c) world's first decay ratio image (reproduced from the paper)

In this study, the team focused on the ratio between three-photon decay and two-photon decay, and utilized the energy-momentum conservation geometric symmetry satisfied by three-photon decay to simplify the complex image reconstruction problem into an analytically tractable quadratic equation. The researchers also developed a gamma-ray measurement system consisting of high-resolution GAGG scintillator arrays and silicon photomultiplier (SiPM) photodetector arrays, which is compatible with clinical PET scanners and offers high energy resolution.

In the experiments, the research team used the existing PET tracer fluorodeoxyglucose (18F-FDG) to image mixed samples of water and the porous material XAD-4. The results showed a significantly elevated positronium ratio in the porous material, allowing the team to obtain three-photon decay ratio images and complete the first validation of the PRI principle.

The research team stated that PRI technology can non-invasively observe microenvironmental information inside organisms or materials, such as pore size and hypoxic status, without adding additional radiation exposure. In the future, this technology is expected to be used for assessing tumor hypoxia in cancer, determining treatment resistance, and supporting early detection of diseases such as Alzheimer's disease.

Furthermore, PRI demonstrates a certain degree of compatibility with the theranostics approach. The research team proposed that if radionuclides with both diagnostic and therapeutic potential, such as 64Cu, are combined with PET and PRI technologies, it may be possible in the future to simultaneously quantify metabolic status and hypoxic environment during tumor treatment, providing more imaging evidence for personalized medicine. The related study, titled "Advancing PET with direct imaging of three-photon decay using pure positron emitters," was published in Communications Physics.