ABSTRACT
Radiation therapy is rapidly evolving toward the delivery of higher dose rates to improve cancer treatment. In vitro experiments were performed to investigate the response of 9L and MCF-7 cancer cell lines, exposed to 10MV X-ray radiations. Up to 8Gy was delivered at a dose-rate of 50cGy/min compared to 5Gy/min. The data obtained emphasizes the importance of taking into account not only the physical, but also the radiobiological parameters, when planning a particular cancer treatment.
Subject(s)
Radiotherapy Dosage , Relative Biological Effectiveness , Cell Survival/radiation effects , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , MCF-7 Cells , Neoplasms/radiotherapy , Radiotherapy, Intensity-ModulatedABSTRACT
The application of nanoparticles (NPs) in radiotherapy is an increasingly attractive technique to improve clinical outcomes. The internalisation of NPs within the tumour cells enables an increased radiation dose to critical cellular structures. The purpose of this study is to investigate, by means of Geant4 simulations, the dose enhancement within a cell population irradiated with a 150kVp photon field in the presence of a varying concentration of tantalum pentoxide (Ta2O5) NP aggregates, experimentally observed to form shells within tumour cells. This scenario is compared to the more traditionally simulated homogeneous solution of NP material in water with the same weight fraction of Ta2O5, as well as to a cell population without NPs present. The production of secondary electrons is enhanced by increased photoelectric effect interactions within the high-Z material and this is examined in terms of their kinetic energy spectra and linear energy transfer (LET) with various NP distributions compared to water. Our results indicate that the shell formation scenario limits the dose enhancement at 150kVp. The underlying mechanism for this limit is discussed.
Subject(s)
Metal Nanoparticles/radiation effects , Metal Nanoparticles/therapeutic use , Oxides , Tantalum , Animals , Biophysical Phenomena , Cell Line, Tumor , Cell Survival/radiation effects , Ceramics , Computer Simulation , Humans , Linear Energy Transfer , Metal Nanoparticles/chemistry , Models, Biological , Monte Carlo Method , Neoplasms/radiotherapy , Photons/therapeutic use , Radiotherapy Dosage , RatsABSTRACT
Despite the use of multimodal treatments incorporating surgery, chemotherapy and radiotherapy, local control of gliomas remains a major challenge. The potential of a new treatment approach called indirect radio-chemo-beta therapy using the synergy created by combining methotrexate (MTX) with bromodeoxyuridine (BrUdR) under optimum energy x-ray irradiation is assessed. 9L rat gliosarcoma cells pre-treated with 0.01 µM MTX and/or 10 µM BrUdR were irradiated in vitro with 50 kVp, 125 kVp, 250 kVp, 6 MV and 10 MV x-rays. The cytotoxicity was assessed using clonogenic survival as the radiobiological endpoint. The photon energy with maximum effect was determined using radiation sensitization enhancement factors at 10% clonogenic survival (SER10%). The cell cycle distribution was investigated using flow cytometric analysis with propidium iodide staining. Incorporation of BrUdR in the DNA was detected by the fluorescence of labelled anti-BrUdR antibodies. The radiation sensitization enhancement exhibits energy dependence with a maximum of 2.3 at 125 kVp for the combined drug treated cells. At this energy, the shape of the clonogenic survival curve of the pharmacological agents treated cells changes substantially. This change is interpreted as an increased lethality of the local radiation environment and is attributed to supplemented inhibition of DNA repair. Radiation induced chemo-beta therapy was demonstrated in vitro by the targeted activation of combined pharmacological agents with optimized energy tuning of x-ray beams on 9 L cells. Our results show that this is a highly effective form of chemo-radiation therapy.
Subject(s)
Bromodeoxyuridine/pharmacology , Glioma/drug therapy , Glioma/radiotherapy , Methotrexate/pharmacology , Photons/therapeutic use , Radiation-Sensitizing Agents/pharmacology , Animals , Antimetabolites, Antineoplastic/pharmacology , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Line, Tumor , Combined Modality Therapy , DNA Repair/drug effects , DNA Repair/radiation effects , Flow Cytometry , Glioma/pathology , Rats , X-RaysABSTRACT
This article pioneers a study into the influence of the high-Z component of nanoparticles on the efficacy of radioprotection some nanoparticles offer to exposed cells irradiated with X-rays. We reveal a significant decrease in the radioprotection efficacy for cells exposed to CeO2 nanoparticles and irradiated with 10 MV and 150 kVp X-rays. In addition, analysis of the 150 kVp survival curve data indicates a change in radiation quality, becoming more lethal for irradiated cells exposed to CeO2 nanoparticles. We attribute the change in efficacy to an increase in high linear energy transfer Auger electron production at 150 kVp which counterbalances the CeO2 nanoparticle radioprotection capability and locally changes the radiation quality. This study highlights an interesting phenomenon that must be considered if radiation protection drugs for use in radiotherapy are developed based on CeO2 nanoparticles. FROM THE CLINICAL EDITOR: CeO2 nanoparticles are thought to offer radioprotection; however, this study reveals significant decrease in the radioprotection efficacy for cells exposed to CeO2 nanoparticles and irradiated with 10 MV and 150 kVp X-rays. This phenomenon must be considered when developing radiation protection drugs based on CeO2 nanoparticles.
