Glioblastoma multiforme (GBM) is at present an incurable disease with a 5-year survival rate of 5.5%, despite improvements in treatment modalities such as surgery, radiation therapy, chemotherapy [e.g., temozolomide (TMZ)], and targeted therapy [e.g., the antiangiogenic agent bevacizumab (BEV)]. Diffusing alpha-emitters radiation therapy (DaRT) is a new modality that employs radium-224-loaded seeds that disperse alpha-emitting atoms inside the tumor. This treatment was shown to be effective in mice bearing human-derived GBM tumors. Here, the effect of DaRT in combination with standard-of-care therapies such as TMZ or BEV was investigated. In a viability assay, the combination of alpha radiation with TMZ doubled the cytotoxic effect of each of the treatments alone in U87 cultured cells. A colony formation assay demonstrated that the surviving fraction of U87 cells treated by TMZ in combination with alpha irradiation was lower than was achieved by alpha- or x-ray irradiation as monotherapies, or by x-ray combined with TMZ. The treatment of U87-bearing mice with DaRT and TMZ delayed tumor development more than the monotherapies. Unlike other radiation types, alpha radiation did not increase VEGF secretion from U87 cells in culture. BEV treatment introduced several days after DaRT implantation improved tumor control, compared to BEV or DaRT as monotherapies. The combination was also shown to be superior when starting BEV administration prior to DaRT implantation in large tumors relative to the seed size. BEV induced a decrease in CD31 staining under DaRT treatment, increased the diffusive spread of 224Ra progeny atoms in the tumor tissue, and decreased their clearance from the tumor through the blood. Taken together, the combinations of DaRT with standard-of-care chemotherapy or antiangiogenic therapy are promising approaches, which may improve the treatment of GBM patients.
The average radon concentration in Israeli dwellings was assessed by combining the results of a 2006 radon survey in single-family houses with the results of a 2011 radon survey in apartments of multistorey buildings. Both surveys were based on long-term measurements using CR-39 detectors. The survey in multistorey buildings was intended to assess the influence of recent practices in the local building industry on the radon concentrations. These practices include the use of building materials with higher concentrations of the natural radionuclides in the last 20 y than before, as well as the improvement in sealing techniques over that period. Another practice in place since the early 1990 s is the building of a shielded area in every apartment that is known as an RSS (residential secure space). The RSS is a room built from massive concrete walls, floor and ceiling that can be hermetically sealed and is intended to protect its residents from a missile attack. The influence of the above-mentioned features on radon concentrations was estimated by dividing the participating apartments into two groups: apartments in buildings >20 y, built using building materials with low concentrations of the natural radionuclides, regular sealing and without an RSS and apartments in buildings newer than 10 y, built using building materials with higher concentrations of the natural radionuclides, improved sealing and including an RSS. It was found that the average radon concentration in apartments in new buildings was significantly higher than in old buildings and the average radon concentration in single-family houses was significantly higher than in apartments in multistorey buildings. Doses due to indoor radon were estimated on the basis of the updated information included in the 2009 International Commission on Radiological Protection statement on radon.
The radiation dose to the population of Israel due to exposure to natural sources of ionizing radiation was assessed. The main contributor to the dose is radon that accounts for 60% of the exposure to natural sources. The dose due to radon inhalation was assessed by combining the results of a radon survey in single-family houses with the results of a survey in apartments in multi-storey buildings. The average annual dose due to radon inhalation was found to be 1.2 mSv. The dose rate due to exposure to cosmic radiation was assessed using a code that calculates the dose rate at different heights above sea level, taking into account the solar cycle. The annual dose was calculated based on the fraction of time spent indoors and the attenuation provided by buildings and was found to be 0.2 mSv. The annual dose due to external exposure to the terrestrial radionuclides was similarly assessed. The indoor dose rate was calculated using a model that takes into account the concentrations of the natural radionuclides in building materials, the density and the thickness of the walls. The dose rate outdoors was calculated based on the concentrations of the natural radionuclides in different geological units in Israel as measured in an aerial survey and measurements above ground. The annual dose was found to be 0.2 mSv. Doses due to internal exposure other than exposure to radon were also calculated and were found to be 0.4 mSv. The overall annual exposure of the population of Israel to natural sources of ionizing radiation is therefore 2 mSv and ranges between 1.7 and 2.7 mSv.
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