Alpha-particle emitting 213Bi-anti-EGFR immunoconjugates eradicate tumor cells independent of oxygenation

Hypoxia is a central problem in tumor treatment because hypoxic cells are less sensitive to chemo- and radiotherapy than normoxic cells. Radioresistance of hypoxic tumor cells is due to reduced sensitivity towards low Linear Energy Transfer (LET) radiation. High LET α-emitters are thought to eradicate tumor cells independent of cellular oxygenation. Therefore, the aim of this study was to demonstrate that the cell-bound α-particle emitting 213Bi immunoconjugates efficiently kill hypoxic just like normoxic CAL33 tumor cells. For that purpose CAL33 cells were incubated with 213Bianti- EGFR-MAb or irradiated with photons with a nominal energy of 6 MeV both under hypoxic and normoxic conditions. Oxygenation of cells was checked via the hypoxia-associated marker HIF-1α. Survival of cells was analysed using the clonogenic assay. Cell viability was monitored with the WST colorimetric assay. Results were evaluated statistically using a t-test and a Generalized Linear Mixed Model (GLMM). Survival and viability of CAL33 cells decreased both after incubation with increasing 213Bi-anti-EGFR-MAb activity concentrations (9.25 kBq/ml – 1.48 MBq/ml) and irradiation with increasing doses of photons (0.5 – 12 Gy). Following photon irradiation survival and viability of normoxic cells were significantly lower than those of hypoxic cells at all doses analysed. In contrast, cell death induced by 213Bianti- EGFR-MAb turned out to be independent of cellular oxygenation. These results demonstrate for the first time that α-particle emitting 213Bi-immunoconjugates eradicate hypoxic tumor cells as effective as normoxic cells. Therefore, 213Biradioimmunotherapy seems to be an appropriate strategy for treatment of hypoxic tumors.JRC.E.5-Nuclear chemistr

How Relevant Is the Parallax Effect on Low Centered Pelvic Radiographs in Total Hip Arthroplasty

The correct cup position in total hip arthroplasty (THA) is usually assessed on anteroposterior low centered pelvic radiographs, harboring the risk of misinterpretation due to projection of a three-dimensional geometry on a two-dimensional plane. In the current study, we evaluate the effect of this parallax effect on the cup inclination and anteversion in THA. In the course of a prospective clinical trial, 116 standardized low centered pelvic radiographs, as routinely obtained after THA, were evaluated regarding the impact of central beam deviation on the cup inclination and anteversion angles. Measurements of the horizontal and vertical beam offset with two different methods of parallax correction were compared with each other. Furthermore, the effect of parallax correction on the accuracy ofmeasuring the cup position was investigated. The mean difference between the two parallax correction methods was 0.2° ± 0.1° (from 0° to 0.4°) for the cup inclination and 0.1° ± 0.1° (from −0.1° to 0.2°) for the anteversion. For a typically intended cup position of a 45° inclination and 15° anteversion, the parallax effect led to a mean error of −1.5° ± 0.3° for the inclination and 0.6° ± 1.0° for the anteversion. Central beam deviation resulted in a projected higher cup inclination up to 3.7°, and this effect was more prominent in cups with higher anteversion. In contrast, the projected inclination decreased due to the parallax effect up to 3.2°, especially in cups with high inclination. The parallax effect on routinely obtained low centered pelvic radiographs is low and not clinically relevant due to the compensating effect of simultaneous medial and caudal central beam deviation

How Relevant Is the Parallax Effect on Low Centered Pelvic Radiographs in Total Hip Arthroplasty

The correct cup position in total hip arthroplasty (THA) is usually assessed on anteroposterior low centered pelvic radiographs, harboring the risk of misinterpretation due to projection of a three-dimensional geometry on a two-dimensional plane. In the current study, we evaluate the effect of this parallax effect on the cup inclination and anteversion in THA. In the course of a prospective clinical trial, 116 standardized low centered pelvic radiographs, as routinely obtained after THA, were evaluated regarding the impact of central beam deviation on the cup inclination and anteversion angles. Measurements of the horizontal and vertical beam offset with two different methods of parallax correction were compared with each other. Furthermore, the effect of parallax correction on the accuracy ofmeasuring the cup position was investigated. The mean difference between the two parallax correction methods was 0.2° ± 0.1° (from 0° to 0.4°) for the cup inclination and 0.1° ± 0.1° (from −0.1° to 0.2°) for the anteversion. For a typically intended cup position of a 45° inclination and 15° anteversion, the parallax effect led to a mean error of −1.5° ± 0.3° for the inclination and 0.6° ± 1.0° for the anteversion. Central beam deviation resulted in a projected higher cup inclination up to 3.7°, and this effect was more prominent in cups with higher anteversion. In contrast, the projected inclination decreased due to the parallax effect up to 3.2°, especially in cups with high inclination. The parallax effect on routinely obtained low centered pelvic radiographs is low and not clinically relevant due to the compensating effect of simultaneous medial and caudal central beam deviation

Down-to-earth coatings: Carbon nanotube paints reduce lightning damage to aircraft

The low conductivity of composite materials used on aircraft, wind turbines etc. can lead to damage by lightning strikes, and conventional paints can aggravate this problem. Carbon nanotubes offer the possibility of producing paints with special electrical properties for this application as well as for electronics use. Studies now being undertaken are outlined and some initial results are presented

Alpha-particle emitting 213Bi-anti-EGFR immunoconjugates eradicate tumor cells independent of oxygenation.

Hypoxia is a central problem in tumor treatment because hypoxic cells are less sensitive to chemo- and radiotherapy than normoxic cells. Radioresistance of hypoxic tumor cells is due to reduced sensitivity towards low Linear Energy Transfer (LET) radiation. High LET α-emitters are thought to eradicate tumor cells independent of cellular oxygenation. Therefore, the aim of this study was to demonstrate that cell-bound α-particle emitting (213)Bi immunoconjugates kill hypoxic and normoxic CAL33 tumor cells with identical efficiency. For that purpose CAL33 cells were incubated with (213)Bi-anti-EGFR-MAb or irradiated with photons with a nominal energy of 6 MeV both under hypoxic and normoxic conditions. Oxygenation of cells was checked via the hypoxia-associated marker HIF-1α. Survival of cells was analysed using the clonogenic assay. Cell viability was monitored with the WST colorimetric assay. Results were evaluated statistically using a t-test and a Generalized Linear Mixed Model (GLMM). Survival and viability of CAL33 cells decreased both after incubation with increasing (213)Bi-anti-EGFR-MAb activity concentrations (9.25 kBq/ml-1.48 MBq/ml) and irradiation with increasing doses of photons (0.5-12 Gy). Following photon irradiation survival and viability of normoxic cells were significantly lower than those of hypoxic cells at all doses analysed. In contrast, cell death induced by (213)Bi-anti-EGFR-MAb turned out to be independent of cellular oxygenation. These results demonstrate that α-particle emitting (213)Bi-immunoconjugates eradicate hypoxic tumor cells as effective as normoxic cells. Therefore, (213)Bi-radioimmunotherapy seems to be an appropriate strategy for treatment of hypoxic tumors

Western blot analysis of HIF-1α expression in CAL33 cells under normoxia and hypoxia.

<p>A) HIF-1α expression at different times (0–24 h) after setup of hypoxia; 3 h+3 h: incubation of cells done twice for 3 hours under hypoxia, interrupted by a 10 min phase under normoxic conditions. B) HIF-1α expression at different times (0–180 min) after release of CAL33 from hypoxia and incubation under normoxic conditions; control: normoxic cells; CoCl₂: cells treated with CoCl₂ used as positive control; 160 K, 105 K, 75 K molecular weight markers (RPN800, GE Healthcare). Unspecific staining of protein bands other than HIF-1α was used as sample loading control.</p

Relative risk for cell survival/viability after irradiation with photons/²¹³Bi-anti-EGFR-MAb under normoxia/hypoxia.

<p>Relative risk (RR) (▪) denotes RR-fold higher survival of CAL33 cells irradiated under hypoxia compared to normoxia. RR was calculated according to the Generalized Linear Mixed Model (GLMM). Overall cell survival/viability is significantly (RR-fold) higher under hypoxia, if the 95%- confidence interval (•) doesn't include the value 1 (red line).</p

Clonogenic survival and viability of normoxic and hypoxic cells after irradiation with photons or ²¹³Bi-anti-EGFR-MAb.

<p>Results of single experiments are shown as pale coloured graphs, results of means as bold coloured graphs. A) Number of clones (clonogenic assay) and B) absorbance (WST viability assay) as a function of activity concentration (²¹³Bi-anti-EGFR-MAb) or photon dose, respectively.</p

International multifocus approach on arousals in children

SCOPUS: ar.jinfo:eu-repo/semantics/publishe