Auger Effect For Cancer Therapy: Application Of Characteristic Photons Derived From A Novel Transmission Type X-Ray Source

Auger effect is an attractive subject in cancer radiotherapy because the Auger electrons have a high energy and short travel distance (<10 nm) in biological matter, which could induce violent damage on biomolecules like DNA. Auger effect can be generated in cancer cells by radionuclide “Auger emitters”, or monochromatic X-Ray on heavy atoms with corresponding K-edge energy. However, biosafety concerns and the requirement of synchrotron accelerator hindered the clinical translation of Auger effect in cancer therapy. The current study aims to develop a novel X-Ray source that can generate characteristic photons similar to synchrotron radiation, applying Auger effect to cancer therapy in pre-clinical and clinical studies. A novel design of transmission type X-Ray tube (denominated “NanoRay”) was developed, which allows electron beams to pass through the metal target and generates characteristic X-Ray photons, according to the Kα of target metal used. Thymidine analogues bromodeoxyuridine (BrdU) and iododeoxyuridine (IdU) were used to label cancer cell DNA, and then combined with NanoRay treatment. The novel design of NanoRay tube substantially minimizes X-Ray generator to be portable, which produces characteristic photons similar to synchrotron radiation. Preclinical studies confirmed a significantly improved anti-tumor outcome when IdU was combined with NanoRay, but not conventional radiation. In vivo tumor treatment combining 33 keV NanoRay and IdU showed a tumor reduction rate >80% as compared to Nanoray alone. In vitro analyses using comet assay and γH2AX staining showed significantly enhanced DNA damages by 2-fold in cancer cells when NanoRay was combined with BrdU or IdU, as compared to NanoRay alone, confirming the impact of Auger effect on cancer DNA. NanoRay represents a novel source of medical X-Ray, holding promise to harness Auger effect in clinic for improved cancer therapy.