Combined IUdR and enriched specific low-energy X-ray irradiation for Auger electron cancer therapy

Objectives 5-iododeoxyuridine (IUdR) is one type of radiosensitizers which can incorporate into DNA during proliferation. Combined IUdR and synchrotron radiation with energy slightly above K-edge of iodine to generate Auger electrons (AE) has been used for cancer therapy. The linear energy transfer (LET) of an AE can be as high as 100 keV/μm which is capable of inducing enormous DNA damage leading to cell death. This study aims to combine IUdR and transmission X-ray tube equipped with Tantalum target (NanoRay) which generates 33-40 keV- enriched photons to induce AE from iodine for cancer therapy.

Methods With different settings, the NanoRay produces X-ray with 10%, 20% and 30% of 33-40 keV- enriched photons. NG4TL4 fibrosarcoma cell line was used in this study. After treatment of IUdR combined with X-ray or Co-60 irradiation, cell survival was measured using colony formation assay, DNA damage was assayed by comet assay and γ-H2AX immunofluorescent staining. Kinetics of intratumorally injected ¹²³IUdR was assessed by SPECT/CT to determine the optimal timing of IR. AE therapy of tumor was carried out by intratumoral injection of IUdR followed by NanoRay irradiation (IR).

Results IUdR+NanoRay IR resulted in higher cell killing effect and DNA damage than IR alone or IUdR alone. IUdR+NanoRay showed better cell killing effect and higher DNA damage than IUdR+Co-60, indicating better therapeutic potential of AE than that of radiosensitization. IUdR+NanoRay with highest proportion of 33-40 keV (30%) induced more severe DNA damage than 20% and 10% settings. IUdR+NanoRay IR significantly inhibited tumor growth as compared to IUdR treatment or NanoRay IR alone.

Conclusions This preliminary study validated the therapeutic effect of AE therapy for cancer by combining IUdR treatment and X-irradiation with enriched 33-40 keV photons, which may possess high potential to be developed for future cancer therapy.