Development of a Novel Proton Therapy Technique Using Resonant Nuclear Reactions: integrated proton-dynamic therapy, iPDT

In a super-aged society, many patients take antithrombotic drugs for atherosclerotic diseases. Even such patients are not infrequently diagnosed with cancer, making the development of minimally invasive cancer treatments highly desirable. Radiation therapy is a non-bleeding treatment. However, it causes damage indiscriminately. Chemotherapy is also often unsuitable for the very elderly due to its secondary adverse events. This report proposes a world-first treatment method, which utilizes carbon beams and alpha particles generated by the resonance nuclear reaction between ¹⁵ N, specifically accumulated in cancer cells, and proton beams. The authors named it as an integrated proton-dynamic therapy, iPDT. This induces ionization effects 50 times greater than proton beams alone locally within the cancer tissue, causing its destruction while causing almost no damage to normal tissue. ¹⁵ N-aminolevulinic acid (ALA) was used for a cancer specific ¹⁵ N delivery. Three hours after the ALA treatment, the cells were irradiated with proton beam. After irradiation, morphological changes in cells were observed using time-lapse imaging. Furthermore, DNA damage induced by proton beam irradiation was evaluated by immunofluorescence staining for γH2AX. These studies revealed that ¹⁵ N delivery via aminolevulinic acid induces ( ¹⁵ N, αγ, 1H), ¹² C nuclear resonance reactions, significantly increasing cell damage compared to proton irradiation alone.