Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers-New Aspects and Revelations.

This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined. The results were used to transfer the applied scheme from external radiation therapy to radionuclide therapy in nuclear medicine. Here, the CL for the activation of the PSs (psoralen and trioxsalen) is generated by the ionizing radiation from rhenium-188 (a high-energy beta-emitter, Re-188). In vitro cell survival studies were performed on FaDu, B16 and 4T1 cells. A characterization of the PSs (absorbance measurement and gel electrophoresis) and the CL produced by Re-188 (luminescence measurement) was performed as well as a comparison of clonogenic assays with and without PSs. The methods of Yoon et al. were reproduced with a beam line at our facility to validate their results. In our studies with different concentrations of PS and considering the negative controls without PS, the statements of Yoon et al. regarding the positive effect of CL could not be confirmed. There are slight differences in survival fractions, but they are not significant when considering the differences in the controls. Gel electrophoresis showed a dominance of trioxsalen over psoralen in conclusion of single and double strand breaks in plasmid DNA, suggesting a superiority of trioxsalen as a PS (when irradiated with UVA). In addition, absorption measurements showed that these PSs do not need to be shielded from ambient light during the experiment. An observational test setup for a PDT nuclear medicine approach was found. The CL spectrum of Re-188 was measured. Fluctuating inconclusive results from clonogenic assays were found.

Combining Cisplatin with Different Radiation Qualities-Interpretation of Cytotoxic Effects In Vitro by Isobolographic Analysis.

BACKGROUND: The combination of platinum-containing cytostatic drugs with different radiation qualities has been studied for years. Despite their massive side effects, these drugs still belong to the therapeutic portfolio in cancer treatment. To overcome the disadvantages of cisplatin, our study investigated the cytotoxic effects of combining radionuclides with cisplatin. METHODS: FaDu cells were treated with cisplatin (concentration ≈ 2 µM) and additionally irradiated after two hours with the alpha-emitter 223Ra, the beta-emitter 188Re as well as external X-rays using dose ranges of 2-6 Gy. Cell survival was followed by colony formation assays and plotted against cisplatin concentration and radiation dose. The results were interpreted by isobolograms. RESULTS: Isobolographic analyses revealed a supra-additive cytotoxic effect for the combination of cisplatin and 223Ra. A sub-additive effect was observed for the combination of cisplatin and 188Re, whereas a protective effect was found for the combination with X-rays. CONCLUSIONS: The combination of cisplatin and 223Ra may have the potential to create a successfully working therapy scheme for various therapy approaches, whereas the combination with 188Re as well as single-dose X-ray treatment did not lead to a detectable radiosensitizing effect. Thus, the combination with alpha-emitters might be advantageous and, therefore, should be followed in future studies when combined with cytostatic drugs.