Indirect radio-chemo-beta therapy: a targeted approach to increase biological efficiency of x-rays based on energy

Abstract

Tehei, M. (2015). Indirect radio-chemo-beta therapy: a targeted approach to increase biological efficiency of x-rays based on energy. Physics in Medicine and Biology, 60 (20), 7847-7859.Indirect radio-chemo-beta therapy: a targeted approach to increase biological efficiency of x-rays based on energy AbstractDespite 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 radiochemo-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 xrays. 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. AbstractDespite 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 (SER 10% ). 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 labeled antiBrUdR 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 energ...

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“…After approximately 15 doubling times, petri dishes were washed with PBS and adherent cell colonies fixed and stained with a 1:3 crystal violet:ethanol solution. Colonies (≥50 cells/colony) were manually counted and presented as Mean Plating Efficiency (MPE; [number of colonies]/[number of cells plated]*100) and Surviving Fraction (SF; MPE of treatment group/MPE of control group) as previously described 49 . Unirradiated control samples (with and without drugs) were handled under the same conditions as the irradiated samples.…”

Thulium oxide nanoparticles as radioenhancers for the treatment of metastatic cutaneous squamous cell carcinoma

“…Within the plate area, colonies were identified as puncta that had a diameter from 0.5-5 mm (containing ≥50 cells, determined by translating average cell size into a colony size of 50 or more cells) (supplementary figure 1(c)) and identified colonies were automatically enumerated. Data are presented as mean PE (number of colonies/number of cells plated * 100) and surviving fraction (SF; PE of treatment group/ PE of control group) as previously described (Oktaria et al 2015). Unirradiated control samples (with and without nanoparticles/drugs) were handled under the same conditions as the irradiated samples.…”

In vitro investigation of the dose-rate effect on the biological effectiveness of megavoltage X-ray radiation doses

“…the ability of a single cell to form colonies in vitro (Puck et al 1956). The method used in this study was derived from previous work (Oktaria et al 2015). Both the control and irradiated cells were plated immediately after the irradiation experiments.…”

“…Measurements of the cell cycle distribution were performed by flow cytometric analysis using propidium iodide (PI) staining. The method used was derived from previous work (Oktaria et al 2015;Vine et al 2007). Cells (2.0 x 10 6 ) were centrifuged at 1500 rpm for 5 min at 4C and washed twice with cold phosphate buffer solution (PBS) (Ca 2+ and Mg 2+ free) then fixed by drop wise addition of 1mL ice-cold ethanol (70%) and stored at -20C for up to 7 days before DNA analysis.…”