In This Field, Three Main Projects Are Currently Underway:

These projects include ultra-high dose rate irradiation (FLASH), the application of photosensitizers as radiosensitizers, and the medical application of laser plasma acceleration. In addition to cancer treatment, which has traditionally been the primary application of radiation therapy, we are also aiming to extend its use to benign conditions such as arrhythmia and arthritis.

1. Elucidating the Role of Lipids at the Cellular and Organ Levels in FLASH Radiotherapy and Developing Novel Lipid-Peptide Therapies

(This study is conducted in collaboration with Professor Mitsutoshi Setou (Hamamatsu University School of Medicine) and the Institut Curie (France), as part of an international research program supported by the Japan Agency for Medical Research and Development (AMED) under the ASPIRE initiative.)

Radiation therapy, a key pillar of cancer treatment, has made significant advances in precision and in reducing damage to healthy tissues. FLASH radiotherapy, which involves ultra-high dose rate irradiation, has demonstrated a unique "FLASH effect" that spares normal tissue while maintaining tumor control. However, the mechanisms underlying this effect remain unclear. Recent studies suggest that lipid metabolism may play a critical role. Furthermore, lipid-mediated post-translational modification (LPTM) has emerged as a key regulator of cellular stress responses, including those induced by radiation. This project aims to investigate lipid alterations and the role of LPTM in both conventional (CONV) and FLASH radiotherapy, with the ultimate goal of improving treatment outcomes.

2. Development of a Treatment for Refractory Brain Tumors Using X-ray-Activated Photodynamic Effects

While radiation therapy is one of the three major cancer treatments, certain types of cancer--such as glioblastoma--remain resistant to current methods. Though various radiosensitizers, including those that enhance the oxygen effect, have been explored, none have yet been established as standard treatments. Meanwhile, light-based therapies such as photodynamic therapy (PDT) and photoimmunotherapy have been applied clinically, but are limited by the inability to deliver light to deep-seated tumors. To overcome this limitation, we are exploring an innovative method that directly excites photosensitizers using highly penetrating X-rays. Through screening studies, we have identified candidate compounds for X-ray-activated photosensitizers. This research represents a novel approach, leveraging Japan's world-leading expertise in photosensitizer technology, to develop an effective treatment for refractory brain tumors.

3. Development of Fiber-Based Laser-Accelerated Radiation Therapy for Refractory Arrhythmias

Catheter ablation is a well-established standard treatment for arrhythmias. However, for refractory arrhythmias such as ventricular tachycardia (VT), recurrence rates remain high--about 50%--highlighting the need for better solutions. Recently, cardiac radioablation (CRA), which uses radiation to treat arrhythmias, has shown promising results, outperforming traditional methods in treating VT. Nonetheless, current CRA methods rely on external beam irradiation, which unavoidably exposes surrounding healthy tissue and carries risks such as radiation pneumonitis and secondary cancers.

To address these issues, we propose a novel approach: fiber-based laser-accelerated radiation delivered locally from the tip of a catheter. This method allows precise control of electron beam penetration depth, minimizing collateral damage to nearby tissues. Because the procedure can be performed similarly to existing catheter ablation techniques, it is expected to be easily adopted in clinical practice.

This project aims to develop an innovative medical device that integrates laser-accelerated radiation delivery into catheters, enabling precise CRA through intravascular approaches. By utilizing cutting-edge laser plasma acceleration technology, we aim to achieve localized irradiation from the catheter tip--a breakthrough compared to conventional RF accelerators, which require tens of centimeters for acceleration. This advancement could enable a safer and more effective treatment for refractory arrhythmias, while minimizing damage to healthy tissue.