Abstract 3941: Novel cancer therapy approach based on Auger effect mediated by monoenergetic x-ray
Authors: Erh-Hsuan Lin, Wen-Wong Kuo, Wan-Ting Tseng, Chi-Chieh Cheng, Shih-Feng Tseng, Wei-Li Chen, Chia-Gee Wang, Cheng-Wen Wu
Journal: Cancer Research (2019)

Abstract The Auger effect is a physical phenomenon in which the filling of an inner-shell vacancy of an atom is accompanied by the emission of an electron from the same atom. An Auger electron is estimated to have a travel distance around 2-100 μm, within which an energy up to 106 gray is released. Therefore, if Auger effect can be induced in cancer cell DNA, it could mediate immense damage concentrated in cancer genome, providing a potential approach for cancer therapy. Auger effect can be induced by radioactive isotope itself, like 125I, or monoenergetic X-Ray in combination with specific heavy atom. Conventionally, monoenergetic X-Ray can be produced only in a synchrotron radiation accelerator, which hinders its application in medical use. Here, our study showed that a novel design of X-Ray tube allowing electron beams to pass through the target metal can generate monoenergetic X-ray efficiently. This design substantially minimizes the size of X-Ray generator to be portable, and can generate 3-fold higher X-Ray production than traditional X-ray tube under the same voltage and current-exposure time. The monoenergetic X-Ray generated by the novel design (denominated as NanoRay hereafter) contains &amp;gt;20% of K-characteristic photon, up to 29-fold higher than traditional X-Ray in the same energy range. For anti-cancer analysis, 14 and 33 keV NanoRays were combined with Thymidine analogues BrdU and IdU, respectively, in cancer cell treatment. The results showed that while single treatments showed low cytotoxicity, the combination of Nanorays with BrdU or IdU induced significant cancer cell death synergistically in vitro. In contrast, combined treatments of conventional radiation with BrdU or IdU did not show any synergistic effect. In vivo tumor treatment combining 33 keV NanoRay and IdU showed a tumor reduction rate up to 80% as compared to Nanoray alone. Likewise, combination of conventional radiation with IdU showed no synergistic anti-tumor effect. DNA damage analysis found that NanoRay produced 2-fold more double-strand breaks (DSBs) in cancer cells incorporating BrdU or IdU than control cells, validating the Auger effect induced and applied in cancer genome damage. In summary, the current study presents that NanoRay, a new generation of medical X-Ray with highly specific monoenergetic spectrum, can be generated from a transmission tube within a portable apparatus. When NanoRay is applied to cancer DNA incorporating specific heavy atoms, such as BrdU or IdU, it induced significantly more pronounced DNA DSBs and cell death through Auger effect, thus lowering the dose necessary for corresponding anti-tumor effect induced by conventional radiation. NanoRay serves as a novel medical X-Ray source with low dose, low cost, and high efficiency, holding great promise in future cancer therapy. Citation Format: Erh-Hsuan Lin, Wen-Wong Kuo, Wan-Ting Tseng, Chi-Chieh Cheng, Shih-Feng Tseng, Wei-Li Chen, Chia-Gee Wang, Cheng-Wen Wu. Novel cancer therapy approach based on Auger effect mediated by monoenergetic x-ray [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3941.