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2-Methoxyestradiol. 2-Methoxyestradiol (2-ME) is an endogenous estradiol metabolite that disrupts microtubule function, suppresses murine tumors, and inhibits angiogenesis. Since some microtubule inhibitors have been shown to alter radiosensitivity, we have evaluated 2-ME as a radiation enhancer in vitro. H460 human lung cancer cells were plated, treated with 2-ME for 24 h, and irradiated; then colony-forming ability was assessed. The radiation dose enhancement ratios (DERs) using this protocol were 1.3, 1.8 and 2.1 for 1, 1.5 and 2 microM 2-ME, respectively. Using a single-cell plating protocol, the respective DERs were 1.2, 1.5 and 1.8. The parent compound of 2-ME, beta-estradiol, did not enhance radiation effects at equally cytotoxic doses. Isobologram analysis showed that 1 microM 2-ME was additive with radiation, but that 1.5 and 2 microM were synergistic. Cell cycle analysis showed a dose-dependent increase in the percentage of cells in the radiosensitive G(2)/M phase after a 24-h treatment with 2-ME; a threefold increase in the percentage of cells in G(2)/M phase was observed using 2 microM 2-ME. Treatment with 2 microM 2-ME almost completely inhibited repair of sublethal damage (SLD) as shown using split-dose recovery. Radiosensitive, repair-deficient murine SCID (severe combined immunodeficient) cells did not show enhancement of radiation effects with 2 microM 2-ME, but enhancement was observed in the wild-type parental cells (CB-17). SCID cells complemented with human DNA-dependent protein kinase restored radioenhancement by 2-ME. In addition, MCF-7 breast cancer cells were also radiosensitized by 2 microM 2-ME (DER = 2.1). These data suggest that 2-ME is a potential radiation sensitizer, in addition to its previously reported antitumor and antiangiogenic properties. We have verified the antiangiogenic activity of 2-ME in vitro using human endothelial cells. Based on these results, we hypothesize that the mechanism of radiation enhancement may involve redistribution of cells into G(2)/M phase by 2-ME, and that the resulting population of cells is repair-deficient and thus radiosensitive.
OBJECTIVE - To compare polytomography (PT) and computed tomography (CT) for visualizing fractures and arthrodeses, with and without metal hardware, to determine whether CT could adequately replace PT.
DESIGN AND PATIENTS - An ex vivo bovine model containing fractures in three planes, reduced with metal hardware, was created to compare fractures using PT and CT. The radiation dose at the skin surface was calculated for both examinations. For in vivo assessment, images of 14 patients who underwent both PT and CT (15 fractures, five arthrodeses) were coded, sorted, and independently read by four musculoskeletal radiologists. They rated the degree of certainty of their assessment. Time factors for patients and personnel and financial costs were also compared.
RESULTS - In the ex vivo model the fractures were well seen on both PT and CT. The radiation dose was higher for PT than for CT. In vivo, the degree of certainty in assessment of fractures and arthrodeses was higher for PT than CT in studies in which metal hardware was present, but there was no significant difference in studies without metal hardware or in the combined (with and without hardware) studies. The patient's and technologist's time required to perform a PT examination was greater than that for CT.
CONCLUSION - In the assessment of fractures and arthrodeses containing metal hardware, PT is recommended. For studies without hardware, CT is equivalent and can replace PT.
A newly developed method of radiation dosimetry makes use of the optical properties of polymer gels. The dose-response mechanism relies on the production of light-scattering polymer micro-particles in the gel at each site of radiation absorption. The scattering produces an attenuation of transmitted light intensity that is directly related to the dose and independent of dose rate. For the BANG polymer gel (bis, acrylamide, nitrogen, and gelatin) the shape of the dose-response curve depends on the fraction of the cross-linking monomer in the initial mixture and on the wavelength of light. At 500 nm the attenuation coefficient (mu) increases by approximately 0.7 mm-1 when the dose increases from 0 to 5 Gy. The refractive index of an irradiated gel shows no significant dispersion in the visible region and depends only slightly on the dose. Turbidity difference spectra are compared with theoretical spectra of efficiency factors for total scattering, derived using Mie-Debye theory, and the average sizes of the cross-linked particles produced by radiation, as a function of dose, are established. The particle sizes increase with dose and reach approximately the wavelength of red light. The dependence of the particle sizes on cross-linker fraction parallels a similar dependence of the water proton NMR transverse relaxation rate dose response.
A new method of dosimetry of ionizing radiations has been developed that makes use of tissue-equivalent polymer gels which are capable of recording three-dimensional dose distributions. The dosimetric data stored within the gels are measured using optical tomographic densitometry. The dose-response mechanism relies on the production of light scattering microparticles which result from the polymerization of acrylic comonomers dispersed in the gel. The attenuation of a collimated light beam caused by scattering in the irradiated optically turbid medium is directly related to the radiation dose over the range 0-10 Gy. An optical scanner has been developed which incorporates an He-Ne laser, photodiode detectors, and a rotating gel platform. Using mirrors mounted on a translating stage, the laser beam scans across the gel between each incremental rotation of the platform. Using the set of optical density projections obtained, a cross sectional image of the radiation field is then reconstructed. Doses in the range 0-10 Gy can be measured to better than 5% accuracy with a spatial resolution approximately 2 mm using the current prototype scanner. This method can be used for the determination of three-dimensional dose distributions in irradiated gels, including measurements of the complex distributions produced by multi-leaf collimators, dynamic wedge and stereotactic treatments, and for quality assurance procedures.
A new type of tissue-equivalent medium for magnetic resonance imaging of the dose distributions produced by ionizing radiation has been developed. Agarose gel is infused with acrylamide and N,N'-methylene-bis-acrylamide (Bis) comonomers, which are readily polymerized by free radical initiators in de-aerated aqueous solutions. Polymerization and cross-linking induced locally by free radical products of water radiolysis increase the rate of water proton spin relaxation gradually up to doses of about 15 Gy. The slopes of the dose-response curves at 64 MHz are 0.015 and 0.28 s-1 Gy-1 for R1 and R2, respectively. The agarose matrix as well as the high (50% by weight) relative concentration of the cross-linker (Bis) per total comonomer limit the spread of polymerization so that the spatial distribution of the radiation dose is faithfully represented in the resultant spatial distribution of relaxation rates. The gel can be imaged with conventional magnetic resonance imaging devices with high spatial resolution and accuracy. In addition, due to the well established effect of the precipitation of insoluble agglomerates of highly cross-linked acrylamide, the optical turbidity of the gel increases gradually with the absorbed dose. This may provide an additional means of visualizing the dose distribution in three dimensions. The major advantage of the acrylamide-Bis-agarose gels over those that depend on ionic chemical dosimeters, for example, Fricke-infused gels, lies in the lack of diffusion of radiation-induced chemical changes subsequent to or concurrent with irradiation.
Chinese hamster ovary (CHO) cells, in either exponential growth or unfed plateau phase were exposed to graded doses of radiation from Iodine-125 or from Cesium-137 at various dose-rates and the cells were assayed for reproductive integrity. From the patterns of cell survival obtained, the relative biological effectiveness (RBE) of the emission from 125I was determined relative to 137Cs. The RBE determined using cells in exponential growth was found to have a value of about 1.2, which was independent of the level of cell survival and did not vary over the dose-rate range from 7.5 to 53 cGy/hr. Using plateau phase cells the RBE has a constant value of about 1.3 between 13 to 46 cGy/hr, but is closer to 2.0 at lower dose-rates of 5 to 7 cGy/hr.
Apparatus and dosimetry techniques have been developed which make possible studies of the biological effects of radiation from encapsulated 125I sources at clinically relevant dose rates using mammalian cells attached to culture dishes. The variation of dose rate from 125I photons as a function of distance from the interface between different materials was investigated. A polystyrene substrate changes the mean dose rate in attached cells by about 21%, depending on cell thickness. To reduce dosimetry uncertainty caused by this effect, special petri dishes were made from polyvinylidene fluoride, which changes the mean dose in attached cells by only 10%. Chinese hamster ovary cells attached to these dishes were cultured in incubators which contained 125I and 137Cs sources, allowing the effects of various dose rates (.005 to 0.80 Gy/hr) of radiation from the two isotopes to be compared. The relative dose rates from these low- and high-energy photons were measured with an accuracy of +/- 7% or better using an air-equivalent ionization chamber designed to resemble one of our special petri dishes. Calculations of dose rates from 125I give values within 4% of the measured dose rates used to determine the relative biological effectiveness of 125I photons.