A Novel Cancer Therapy Using Proton Beam: An Integrated Proton-Dynamic Therapy, iPDT

[Background and Aims] A super-aged society, the prime example of which is Japan, is being flooded with increasing in numerous numbers of aged cancer patients, who often take anti-coagulant medicines to prevent the attacks of ischemic heart diseases and/ or strokes. Since they show bleeding tendency induced by the medicines, it’s hard for them to receive surgical operations. Thus, low invasive cancer treatments without bleedings are abundantly desired. In this study, the applicant will establish a new proton therapy, in which a resonance nuclear reaction (RNR) induced by collision of a proton with a stable nitrogen isotope ( 15 N), can be a clue to injure cancer-cells specifically. The LET of the product ions ( 12 C 6+ , 4 He 2+ ) of the 15 N RNR is above 50 times in comparison with the LET of proton. To establish the cancer-specific 15 N delivery, 15 N-aminolevulinic acid ( 15 N-ALA) will be used. This reagent has been already used and obtained regulatory approvals as a diagnostic medicine for the location of the glioblastoma in Japan. [Methods] In this study, a pair of rat gastric epithelial cells, one is normal cell RGM1, and another is cancerous characteristics cells RGK1 were used. The authors treated these cells with both 1mM 15 N-ALA and 14 N-ALA. Thereafter, we measured and compared porphyrin fluorescent intensity of these cells. Moreover, these cells will be irradiated with 4 nc proton beam generated by an electrostatic accelerator, then 4.43 MeV gamma-rays will be measured to demonstrate the amount of 15 N collected specifically in the tumour cells. After these proton irradiations, cells were stained with hoechest33258 and dapi to observe cellular apoptosis. [Results] Cancer cells accumulated 9 folds of 15 N in comparison with normal epithelial cells. After 3hours of proton irradiation, both cancer cells and normal cells were not injured. However, almost all cancer cells were died with apoptosis while normal cells showed few cellular injuries after 24 hours. [Conclusions] Cancer cells were completely killed by RNR involved with imM 15N-ALA and 4nc proton irradiation whereas this dose of proton showed few effects of ionizing radiation on normal cells. Thus, iPDT should be an ideal treatment for cancer. Moreover, the quantitative analysis of 15 N in the tumour cells can be a new pre-diagnosis for iPDT.