Toward new frontiers : Encounter and synergy of state-of-the-art astronomical detectors and exotic quantum beams

Program C01-5	Development of new cancer therapy using compound activation by hard X-rays
Principal Investigator	OGAWA, Mikako (Hokkaido University)

Photoimmuno therapy (PIT) is a new cancer therapy, which has been approved in Japan in September 2020. It uses a photoreactive drug, IR700, conjugated to an antibody that binds to cancer cells. After the drug is administered to the body, the tumor site is irradiated with near-infrared light (690 nm) to kill the cancer cells. We found that the basis of this therapy is the chemical structural change (cleavage of water-soluble axial ligands) of IR700 induced by near-infrared light. As the mechanism of axial ligand cleavage, it was clarified that IR700 receives an electron and becomes an anion radical, and the chemical bond cleavage reaction occurs from this active species.

In this study, we aim to develop a method of activation by hard X-rays, which have high biological permeability. In particular, we will focus on the initial process of radical formation and the inner-shell excitation. We will develop molecules that react more readily with water-generated radicals, such as hydrated electrons and hydroxyl radicals. Or, if we use molecules that generate radicals more easily than water, we may be able to activate compounds by direct radicalization at a level where radicalization of water does not occur. We also believe that chemical bond-selective activation of compounds may be possible using inner-shell excitation and subsequent Auger transitions. The inner-shell excitation is based on the energy difference between the nucleus and mainly K-shell electrons and occurs in soft X-rays, but soft X-rays do not penetrate living organisms. So, we are planning to use inner-shell excitation using secondary radiation (fluorescent X-rays and secondary electrons) generated by scattering and absorption of hard X-rays.

Taking advantage of the characteristics of the research area “quantum beam,” we will focus on theoretical molecular design based on the initial processes of radiation chemistry and the perspective of quantum physics.

Members

Reference Materials

• M. Kobayashi, M. Harada, H. Takakura, K. Ando, Y. Goto, T. Tsuneda, M. Ogawa, T. Taketsugu, “Theoretical and experimental studies on the near-infrared photoreaction mechanism of a silicon phthalocyanine photoimmunotherapy dye: photoinduced hydrolysis by radical anion generation,” Chempluschem 85(9), 1959–1963 (2020).
• K. Sato, K. Ando, S. Okuyama, S. Moriguchi, T. Ogura, S. Totoki, H. Hanaoka, T. Nagaya, R. Kokawa, H. Takakura, M. Nishimura, Y. Hasegawa, P. L. Choyke, M. Ogawa, H. Kobayashi, “Photoinduced ligand release from a silicon phthalocyanine dye conjugated with monoclonal antibodies: a mechanism of cancer cell cytotoxicity after near-infrared photoimmunotherapy,” ACS Cent. Sci. 4(11), 1559–1569 (2018).