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

• Main Authors: Roswitha Runge (Author), Falco Reissig (Author), Nora Herzog (Author), Liane Oehme (Author), Claudia Brogsitter (Author), Joerg Kotzerke (Author)
• Format: Book
• Published: MDPI AG, 2023-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph16121720; 1424-8247
• Keywords: cisplatin; radionuclides; alpha-emitter; cancer therapy; combined treatment; isobolograms; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 16, Iss 12, p 1720 (2023)

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.