Cobalt-60 Γ-rays Research Articles

Response of the FBX aqueous chemical dosimeter to high energy proton and electron beams used for radiotherapy research

The response of the FBX aqueous chemical dosimeter to 10 MeV electron and 100 MeV proton beams was investigated, and the results were compared with those obtained for cobalt-60 gamma rays over a dose range of 0–30 Gy. The sensitivities of the FBX dosimeter in which the absorbance values were measured at the wavelength of maximum absorption (λmax) and 548 nm are approximately the same and amount to 0.091, 0.088, and 0.081 Gy-1 for 10 MeV electrons, cobalt 60 γ-rays, and 100 MeV proton beams, respectively. The corresponding calibration coefficients are 10.99, 11.36, and 12.35 Gy, in their respective order. The molar absorption coefficients that were calculated for cobalt-60 gamma rays amount to 17824 ± 560, 16417 ± 248, and 17694 ± 437 M−1cm−1 at the wavelengths λmax, 540 nm, and 548 nm, respectively. The radiation chemical yield-G (Fe3+) at the wavelengths of λmax and 548 nm has approximately the same values and amounts to 51.1 × 10−7, 49.4 × 10−7, and 45.4 × 10−7 mol.J−1 for 10 MeV electrons, cobalt-60 γ-rays, and 100 MeV proton beams, respectively, and both of them are lower by ∼ 8% than that obtained at the wavelength of 540 nm. A linear response of the FBX dosimeters prepared in the current study was achieved up to 12 Gy, compared with the linear response up to 5 Gy reported in the previous literature. Furthermore, by measuring the absorbance values at the wavelength of the isobestic point, i.e., 555 nm, the linearity of the FBX dosimetric solution may be extended to cover the entire dose range used, i.e., 0.2–30 Gy. Consequently, with good reproducibility (less than 1%), the prepared FBX dosimeter can be utilized for radiotherapy research over the dose range of 0.2–30 Gy.

Total ionizing dose effects of 60Co-γ ray radiation on SiC MOSFETs with different gate oxide thickness

The application of SiC power devices in the space radiation environment not only requires good resistance to Single Event Effect (SEE) but also requires certain resistance to Total Ionizing Dose (TID) and long-term reliability. Increasing the thickness of the gate oxide layer (tox) can effectively improve the ability of SiC VDMOS to resist SEE. However, it will mainly impact its resistance to TID and Gate Oxide Integrity (GOI). Therefore, this paper compares the influence of tox on the radiation resistance and long-term reliability of SiC VDMOS under the same process and irradiation conditions. The experimental results show that after being irradiated by Cobalt-60 γ-rays, the static parameters of SiC VDMOS devices degrade severely with the increase of the tox; at the same time, the thick gate oxide process will also cause more defects in the gate oxide, leading to the decrease of the gate oxide long-term reliability, but it can be significantly improved after high temperature (HT) accelerated annealing. The research results suggest that the method of increasing tox should take into account the requirements of TID resistance and long-term reliability when improving the SEE radiation resistance of SiC VDMOS. This study is based on the improvement of electrical parameters and the analysis of reliability degradation of SiC VDMOS, providing experimental data support for determining the balance point of tox.

Experimental investigation into impacts of neutron irradiation on pMOS dosimeter behaviors

The p-channel metal–oxide–semiconductor (pMOS) transistor is a frequently used dosimeter for ionizing radiation, such as γ-rays, since its threshold voltage changes (ΔVth) in proportion to the ionization dose. When a pMOS is subjected to γ-ray and neutron radiation fields, the neutrons can influence the ΔVth response to γ-rays. Individual cobalt-60 γ-ray irradiation and sequential irradiation by fission neutrons and subsequent cobalt-60 γ-rays are used to explore the neutron-induced impacts. Experiments show that preceding neutron irradiation can reduce γ-ray sensitivity of ΔVth while accelerating the recovery of ΔVth during the post-γ-irradiation annealing. Additionally, the component of ΔVth induced by oxide charges (ΔVox) is separated from that induced by interface traps as determined by mid-gap tests. This proves that the neutron sensitivity of ΔVox accounts for that of ΔVth. According to nuclear collision theory, this work suggests that the electronic loss of neutrons rather than the nuclear loss dominates the neutron-induced influences on ΔVth.

Scavenging of “dry” electrons prior to hydration by azide ions: effect on the formation of H2 in the radiolysis of water by 60Co γ-rays and tritium β-electrons

In this study, we use Monte Carlo track chemistry simulations to show that “dry” secondary electrons, precursors of the “hydrated” electron (e−aq), can be scavenged on the sub-picosecond time scale prior to hydration, by a high concentration (>0.1–1 M) of azide ions (N3−) in water irradiated with 60Co γ-rays and tritium β-electrons at 25 °C. This is a striking result, as N3− is known to react very slowly with e−aq. These processes tend to significantly reduce the yields of H2 as observed experimentally. For both energetic Compton electrons (“linear energy transfer”, LET ∼ 0.3 keV/µm), which are generated by the cobalt-60 γ-rays, and 3H β-electrons (LET ∼ 6 keV/µm), our H2 yield results confirm previous Monte Carlo simulations, which indicated the necessity of including the capture of the precursors to e−aq. Interestingly, our calculations show no significant changes in the scavenging of “dry” electrons at high azide concentrations in passing from γ-radiolysis to tritium β-radiolysis (i.e., with LET). This led us to the conclusion that the higher H2 yield observed experimentally for 3H β-electrons compared with 60Co γ-rays is mainly explained by the difference in the radiation track structures during the chemical stage (>1 ps). The higher LET of tritium β-electrons leads to more molecular products (H2 in this case) in tritium radiolysis than in γ-radiolysis. Finally, a value of ∼0.5 nm was derived for the reaction distance between N3− and the “dry” electron from the H2 yields observed in 60Co γ-radiolysis at high N3− concentrations.

Effects of radiation quality and dose rate on radiation-induced nucleoplasmic bridges in human peripheral blood lymphocytes

Previous studies showed that the yield of cobalt-60 γ-rays-induced nucleoplasmic bridges (NPB) in human peripheral blood lymphocytes is dose dependent. However, the influence of the radiation quality and dose rates on NPB frequencies has not been investigated. The present study aimed to investigate NPB frequencies in human peripheral blood lymphocytes induced by carbon ions and explore the dose rate effect on cobalt-60 γ-rays-induced NPB. To establish dose-response curves, human peripheral blood samples were irradiated with 0, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0 and 8.0 Gy of carbon ions at a dose rate of 3.0 Gy/min in vitro. To explore the dose rate effect, human peripheral blood samples were irradiated with 2.0 and 5.0 Gy of cobalt-60 γ-rays at dose rates of 0.2, 0.5, 1.0, 3.0, 5.0 and 10.0 Gy/min in vitro. NPB and micronuclei (MN) in binucleated cells were analyzed with the cytokinesis-block micronucleus cytome assay. Results showed that the dose-response curve of carbon ion-induced NPB frequencies follow a linear-quadratic model (R2 = 0.934). The relative biological effectiveness (RBE) values of carbon ions to cobalt-60 γ-rays decreased with increased NPB frequencies (ranging from 2.47 to 5.86). Compared with group 1.0 Gy/min, the NPB frequencies in groups 10.0 Gy/min (2.0 Gy), 5.0 and 10.0 Gy/min (5.0 Gy) were decreased significantly (P < 0.05). Carbon ion-induced NPB in human peripheral blood lymphocytes have a good dose-response relationship. Cobalt-60 γ-rays-induced NPB frequencies are affected by the specific dose rate.

Independent reaction times method in Geant4‐DNA: Implementation and performance

The simulation of individual particle tracks and the chemical stage following water radiolysis in biological tissue is an effective means of improving our knowledge of the physico-chemical contribution to the biological effect of ionizing radiation. However, the step-by-step simulation of the reaction kinetics of radiolytic species is the most time-consuming task in Monte Carlo track-structure simulations, with long simulation times that are an impediment to research. In this work, we present the implementation of the independent reaction times (IRT) method in Geant4-DNA Monte Carlo toolkit to improve the computational efficiency of calculating G-values, defined as the number of chemical species created or lost per 100eV of deposited energy. The computational efficiency of IRT, as implemented, is compared to that from available Geant4-DNA step-by-step simulations for electrons, protons and alpha particles covering a wide range of linear energy transfer (LET). The accuracy of both methods is verified using published measured data from fast electron irradiations for • OH and for time-dependent G-values. For IRT, simulations in the presence of scavengers irradiated by cobalt-60 γ-ray and 2MeV protons are compared with measured data for different scavenging capacities. In addition, a qualitative assessment comparing measured LET-dependent G-values with Geant4-DNA calculations in pure liquid water is presented. The IRT improved the computational efficiency by three orders of magnitude relative to the step-by-step method while differences in G-values by 3.9% at 1μs were found. At 7ps, • OH and yields calculated with IRT differed from recent published measured data by 5%±4% and 2%±4%, respectively. At 1μs, differences were 9%±5% and 6%±7% for • OH and , respectively. Uncertainties are one standard deviation. Finally, G-values at different scavenging capacities and LET-dependent G-values reproduced the behavior of measurements for all radiation qualities. The comprehensive validation of the Geant4-DNA capabilities to accurately simulate the chemistry following water radiolysis is an ongoing work. The implementation presented in this work is a necessary step to facilitate performing such a task.

Identification of the differentially expressed protein biomarkers in rat blood plasma in response to gamma irradiation

Purpose: Simple, rapid and high-throughput dose assessment is critical for clinical diagnosis, treatment and emergency intervention in a large-scale radiological accident. The goal of this study is to screen and identify new ionizing radiation-responsive protein biomarkers in rat plasma.Materials and methods: Sprague-Dawley rats were exposed to single doses of 0, 1, 3, 5 Gy of Cobalt-60 γ-rays total body irradiation at a dose rate of 1 Gy/min. The tandem mass tag labeling (TMT) combined with liquid chromatography mass spectrometry (LC-MS/MS) approach was used to screen the differentially expressed proteins in rat plasma collected at 1, 3, 5 and 7 days post-irradiation. Bioinformatics analysis was conducted to explore the biological functions of these proteins. The expression levels of candidate radiation-sensitive protein biomarkers were confirmed using enzyme-linked immune-sorbent assay (ELISA).Results: A total of 503 differentially expressed proteins were identified. Most of these proteins were implicated in immune response, phagocytosis and signal transduction following ionizing radiation. Five up-regulated proteins including alpha-2-macroglobulin (A2m), chromogranin-A (CHGA), glutathione pertidase 3 (GPX3), clusterin (Clu) and ceruloplasmin (Cp) were selected for ELISA analysis. It was found that the expression levels of A2m, CHGA and GPX3 protein were increased in a dose-dependent manner at 1, 3 and 5 days after irradiation.Conclusion: Proteomics analysis revealed radiation-induced differentially expressed proteins in rat plasma. Our results suggested that A2m, CHGA, GPX3 protein expressions alterations in rat plasma may have potential as biomarkers to evaluate radiation exposure.

The effect of bismuth nanoparticles in kilovoltage and megavoltage radiation therapy using magnetic resonance imaging polymer gel dosimetry

Overcoming the tumor radioresistance along with protecting the adjacent normal tissues is considered as the ultimate goal of the radiation therapy. To achieve this goal, extensive studies have demonstrated the radiosensitization potential of the gold nanoparticles (AuNPs) during treatment with low-energy ionizing radiation due to their high-photoelectric absorption coefficient. Compared to the AuNPs, the bismuth nanoparticles (BiNPs) with higher atomic number, low cost, high biocompatibility and high biodegradability are attractive candidates for amplifying the radiation dose. Accordingly, the aim of this study was to quantify dose enhancement factors (DEFs) from BiNPs compared to AuNPs at clinically relevant energies. To quantitatively monitor the three-dimensional distribution of the absorption dose, we synthesized the nPAG polymer gel impregnated with 0.2 mM (0.04 mg/ml tissue) of AuNPs and BiNPs separately. In parallel, the samples were exposed to iridium-192 internal (380 keV) and cobalt-60 external (1.25 MeV) sources to explore the effect of energy. Finally, the R2-weighted dose maps of the calibration and test tubes were acquired by a Siemens 1.5 T MRI scanner. The mean dose enhancements obtained by AuNPs and BiNPs following irradiation of iridium-192 source were 14.72% ± 0.34 and 16.35% ± 0.38, respectively. Conversely, these values decreased to less than 4% for the samples irradiated with cobalt-60 γ-rays. Taken together, our experimental results suggest BiNPs-enhanced iridium-192 brachytherapy can potentially be a promising therapeutic tool in improving the efficacy of cancer radiation therapy. However, enhancement factors obtained from the cobalt-60 source decreased more significantly, highlighting the strong energy dependence of dose enhancement.

Tailored functionalized polymer nanoparticles using gamma radiation for selected adsorption of barium and strontium in oilfield wastewater

To improve oil recovery from oilfield wells mineral scales derived by insoluble BaSO4 and SrSO4 salts during oil extraction should be diminished. In this work, adsorption selectivity of Barium (Ba2+) and Strontium (Sr2+) ions associated with saline formation waters was examined for the first time using nano-sized bi-functional polymer blend synthesized by Cobalt-60 (60Co) γ-rays, as green technology. A bifunctional polymer formed from poly(acrylonitrile)/(styrene-butadiene rubber) homogenous blend is functionalized by -SO3H and -COOH terminal groups (termed as SASB). Those functional groups were selected based on systematic calcium (Ca2+) ions adsorption studies of carboxylate containing molecules. Main and binary interactive effects of solution pH (3–9), adsorbents dose (1-3 g/L), total dissolved salts (TDS, up to 30 g/L), initial Ba2+ and Sr2+ concentrations (10-500 mg/L) and temperature (20–50 oC) on the adsorption selectivity were examined and optimized using Plackett-Burman factorial design (PBD) combined with multiple regression analysis. The regression statistics revealed the significance of quadratic polynomial model to optimize interactive sorption conditions from salty waters with high accuracy level (R2≈ 0.99) rather than linear and two-way interactive models at 95% confidence level. Interestingly finding, the regression and experimental data proved that the presence of up to 10 g/L TDS from alkali metal ions had a significant effect on the enhancement sorption capacity of Ba2+ and Sr2+ when using the prepared sorbent. The SASB adsorbent showed higher sorption selectivity with maximum equilibrium capacity (qmg/g) of 175.3 mg Ba+2 and 210.5 mg Sr+2 per each gram sorbent used in kinetic study. Adsorption kinetics of Ba2+ and Sr2+ sorption by both adsorbents obey pseudo-first and pseudo-second order kinetics, respectively. In sum, the adsorptive power of SASB sorbent is found to be in reverse order of the electronegativity and the hydration radii of the metal ions.

Improved keeping quality of Dendrobium “Bom” orchids using nutrients entrapped in a biodegradable hydrogel

Abstract Poly-γ-glutamic acid (γ-PGA) produced by Bacillus licheniformis TISTR 1010 was blended with polyvinyl alcohol (PVA) and irradiated with cobalt-60 γ-rays to produce hydrogels. The most absorbent hydrogels were formed using a γ-PGA to PVA mass ratio of 90:10 and an irradiation dose of 40 kGy. The optimally made hydrogel had a gelation of 60.3 ± 2.4% and a deionized water absorption of 13.6 ± 0.4 g g−1. These hydrogels filled to capacity with a liquid fertilizer solution were used to make a ‘solid’ fertilizer for potting the Dendrobium “Bom” cut orchids for improving the shelf-life for export. The fertilizer absorption by the hydrogel was 2.0 ± 0.8 g g−1. In deionized water, the prepared solid fertilizer released the nutrient sucrose with average release rates of 0.92 ± 0.01 g L−1 h−1 (measured over a 0–10 h interval) and 0.08 ± 0.00 g L−1 h−1 (measured over a 10–168 h interval). The hydrogel solid fertilizer kept the orchids fresh for ∼8 days at 4 °C and ∼7 days at 25 °C. Relative to liquid fertilizer, the solid fertilizer delayed flower opening by 4 days at 25 °C. Use of a γ-PGA (0.5 g L−1) solution alone also delayed flower senescence and opening. Simple empirical models were shown to satisfactorily predict opening and senescence of flowers with cut stems potted in the solid fertilizer and other media.

Starvation after Cobalt-60 γ-Ray Radiation Enhances Metastasis in U251 Glioma Cells by Regulating the Transcription Factor SP1.

Radiation is of clinical importance during glioma therapy; however, vasculature damage is observed over the treatment course. This type of tissue damage might lead to starvation conditions, affecting tumor metastasis. To test this possibility, we compared starvation conditions in conjunction with radiation treatment to monitor metastatic ability in the U251 glioma cell line. Transcriptome, western blot, and immunofluorescence analyses were used to measure the RNA and protein expression changes of the U251 cells after various treatments. We found that starvation combined with radiation treatment yielded the most significant expression changes in metastasis-related factors compared to that in the control groups. In addition, a metastasis assay was used to directly measure the metastatic ability of the treated cells, which confirmed that the U251 cells treated with starvation combined with radiation possessed the highest metastatic ability. Furthermore, bioinformatics analysis demonstrated that SP1 represented a common transcription factor associated with changes in metastasis-related factors. Blocking SP1 activity by an inhibitor suppressed the starvation-plus-radiation treatment-mediated enhancement of U251 cell metastasis. Our study provides the first evidence that starvation caused by radiation might play a significant role in enhancing the ability of the glioma cell line U251 to metastasize via regulation of the transcription factor SP1.

Characteristics of nucleoplasmic bridges induced by 60Co γ-rays in human peripheral blood lymphocytes

Few studies have shown that the yields of ionising-radiation-induced nucleoplasmic bridges (NPBs) in human cells are dose dependent. However, a dose-response curve between the NPB frequency and the absorbed dose of ionising radiation has not yet been established. This study aimed to investigate NPB frequencies in human peripheral blood lymphocytes induced by cobalt-60 (60Co) γ-rays and to establish a dose-response curve. Human peripheral blood samples were collected from three healthy males, and some of these samples were irradiated with 0-6 Gy 60Co γ-rays. A cytokinesis-block micronucleus cytome assay was then carried out to analyse NPBs and micronuclei (MN) in binucleated cells. The remaining blood samples were irradiated with 0, 2 and 5 Gy of γ-rays, and unstable chromosome aberrations (dicentric chromosome, ring chromosome and acentric chromosome fragment) were analysed. The correlation between NPBs and dicentric plus ring chromosome (dic+r) induced by the same γ-ray dose was also analysed. Results showed that the NPB yields among the three subjects at each dose level were not significantly different. NPBs in binucleated cells at all γ-ray doses conformed to Poisson distribution. The dose-response curve of the γ-ray-induced NPB frequencies followed the linear-quadratic model y = (1.39×10-3)x 2 + (4.94×10-3)x. A positive correlation was observed between the frequencies of NPB and dic+r, as well as between the frequencies of MN and acentric fragments. Therefore, NPB is an important biomarker of early chromosome damage event induced by ionising radiation.

Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation

This study evaluated the clinical and pathologic effects of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the recovery from total body irradiation by comparing it with the effects of granulocyte-colony stimulating factor (G-CSF), an efficacious drug in the treatment of acute bone marrow radiation syndrome. BALB/c mice were treated with G-CSF or hUCB-MSCs after they were irradiated with 7 Gy cobalt-60 γ-rays. Circulating blood counts, histopathologic changes in the bone marrow, and plasma level of Flt-3L and transforming growth factor (TGF-β1) were monitored in the postirradiation period. Hematologic analysis revealed that the peripheral leukocyte counts were markedly increased in the hUCB-MSCs-treated group, whereas G-CSF-treated mice did not recover significantly. Moreover, differential counts showed that hUCB-MSC treatment has regenerative effects on white blood cells, lymphocytes, and monocytes compared with the irradiated group. Treatment with hUCB-MSCs or G-CSF significantly increased immunoreactivity of Ki-67 until 3 weeks after total body irradiation. However, at 3 weeks, the number of Ki-67 immunoreactive cells significantly increased in the hUCB-MSCs-treated group compared with the G-CSF-treated group. Furthermore, hUCB-MSC treatment significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGF-β1, whereas G-CSF treatment failed to decrease the plasma Flt-3L levels at 2 weeks after irradiation. Based on the differences in circulating blood cell reconstitution and cell density of bone marrow, the authors suggest that MSC treatment is superior to G-CSF treatment for hematopoietic reconstitution following sublethal dose radiation exposure.

Enzymatic degradation behavior of silk fibroin fiber treated by γ-ray irradiation

Silk fibroin fiber from Bombyx mori has the advantages of superior tensile strength, non-toxicity, and good biocompatibility. However, its dense crystal structure makes implanted silk fibroin fiber resistant to biodegradation in the body. In the work described herein, silk fibroin fiber was treated with nine different dosages (0−3000 kGy) of Cobalt-60 (60Co) γ-rays, and the degradation performances of the irradiated silk fibroin fibers in collagenase IA (digestion for 30 days) were investigated. The results showed that the degradation leaching rate increased by 25, 35, and 58% at doses of 100, 200, and 500 kGy, respectively, and the diameter was about 62−65% compared with that in the control group. At a dose of 100 kGy, clear degradation stripes appeared on the surface of the silk fibroin fibers, and significantly increased at a dose of 200 kGy. With further increases of 60Co dose, the stripes deepened and turned into cracks. Degradation increased in the amorphous regions of silk fibroin fiber after treatment with γ-rays. With increasing doses of 60Co, degradation also occurred in crystalline areas and the silk II structure was partly converted into silk I. Our studies have shown that appropriate doses (such as 30−500 kGy) of γ-ray pre-treatment on silk fibroin fiber can promote its biological degradation.

The antitumor efficiency of combined electrochemotherapy and single dose irradiation on a breast cancer tumor model

BackgroundThe aim of this study was to investigate the antitumor effectiveness of electrochemotherapy with cisplatin combined with suboptimal radiotherapy doses. Tumor radiosensitization was evaluated on large invasive ductal carcinoma tumors in Balb/C mice.Materials and methodsTumors of an average volume of 630 mm3 were treated with cisplatin, electric pulses, radiotherapy, electrochemotherapy, alone as well as in appropriate combinations. Tumors were irradiated with Cobalt-60 γ-rays at doses 3 Gy and 5 Gy in combination with electrochemotherapy using cisplatin. Controls included each of the treatments alone as well as the combination of the radiotherapy with electric pulses alone or with cisplatin alone. Antitumor effectiveness was evaluated by tumor growth delay, tumor-doubling time, inhibition ratio and the objective response rates.ResultsAs anticipated, electrochemotherapy was more effective than the treatment with cisplatin alone or the application of the electric pulses alone. When treatments were combined with tumor irradiation at either 3 or 5 Gy, the combination with electrochemotherapy was more effective: at 5 Gy, 2 animals out of 8 were in complete remission 100 days later. In general the higher 5 Gy dose of γ-radiation was more effective than the lower one of 3 Gy.ConclusionsThe results of our study demonstrate that irradiation doses, 3 Gy or 5 Gy, increase the antitumor effectiveness of electrochemotherapy with cisplatin on invasive ductal carcinoma tumors. Good antitumor results were achieved in experimental tumors with a size comparable to clinical lesions, demonstrating that this three-modality combined treatment is useful for the treatment of large lesions even at sub-optimal radiotherapy doses.

Hydrogen sorption and radial thermal expansion of bundles of single-walled nanotubes irradiated by γ-rays in hydrogen atmosphere

The influence of radiation exposure in hydrogen atmosphere on the radial thermal expansion of single-walled carbon nanotubes and on their sorption of hydrogen is studied. The irradiation was carried out with cobalt-60 γ-rays (with an energy of 1.2 MeV and an irradiation dose of 1.5·107 rad) in the normal hydrogen atmosphere under pressure 1 atm and at temperature of 300 K. The sorption and desorption of hydrogen by samples of nanotubes were investigated over the temperature range 15–1170 K before and after irradiation. It was found that the irradiation of carbon nanotubes (CNTs) in hydrogen atmosphere leads to considerable increasing an amount of hydrogen sorbed by the sample. The irradiation in hydrogen atmosphere resulted in increasing absolute values of radial thermal expansion of CNTs bundles over the temperature range investigated (2–120 K). The effects of hydrogen physically and chemically sorbed in bundles of CNTs on the radial thermal expansion of the irradiated samples were distinguished.

A TPO Receptor Agonist, ALXN4100TPO, Mitigates Radiation-Induced Lethality and Stimulates Hematopoiesis in CD2F1 Mice

Thrombopoietin (TPO) receptor agonists lacking sequence homology to TPO were designed by grafting a known peptide sequence into the hinge and/or kappa constant regions of a human anti-anthrax antibody. Some of these proteins were equipotent to TPO in stimulating cMpl-r activity in vitro and in increasing platelet levels in vivo. ALXN4100TPO (4100TPO), the best agonist in this series with a K(d) of 30 nM for cMpl-r, exhibited potent activity as a radiation countermeasure in CD2F1 mice exposed to lethal total-body radiation from a cobalt-60 γ-ray source. 4100TPO (2 mg/kg, s.c.) administered once either 24 h before or 6 h after TBI showed superior protection to five daily doses given before or after TBI. Prophylactic administration (69 to 94% survival) was superior to therapeutic schedules (60% survival). 4100TPO conferred a significant survival benefit (P < 0.01) when administered 4 days before or even 12 h after exposure and across a dose range of 0.1 to 8 mg/kg. The dose reduction factors (DRFs) with a single dose of 1 mg/kg 4100TPO 24 h before or 12 h after TBI were 1.32 and 1.11, respectively (P < 0.0001). Furthermore, 4100TPO increased bone marrow cellularity and megakaryocytic development and accelerated multi-lineage hematopoietic recovery in irradiated mice, demonstrating the potential of 4100TPO as both a protector and a mitigator in the event of a radiological incident.

Unexpected skin reaction induced by radiotherapy after chloroquine use

We report a 12-year-old girl who presented with 3 months of left hemiparesis, ataxia, and slurred speech. On examination, she was drowsy, had right-sided sixth-nerve palsy and cerebellar signs. A CT scan revealed an isodense enhancing lesion measuring 3·5×2·2 cm in the posterior fossa, aff ecting the pontine region. MRI examination of the brain confi rmed the CT fi ndings. The lesion was isointense on T1-weighted imaging and had patchy enhancing areas in contrast study. In T2-weighted imaging, the lesion was moderately hyperintense. On the basis of the patients’ clinical features and radiological characteristics, we diagnosed her with a diff use pontine glioma and considered her for direct radiotherapy. Radiotherapy was given by use of parallelopposed bilateral portals in the supine position, with the scalp skin being healthy at this stage. 54 Gy in 30 fractions over 6 weeks was delivered by localised fi elds with a cobalt60 γ-ray unit. When the patient received 36 Gy of treatment, she developed high-grade fever with chills. Her blood count was healthy and she had a negative smear for malarial parasites (vivax, ovale, falciparum, and malariae). Nevertheless, she was given an empirical course of chloroquine consisting of an immediate dose of 500 mg chloroquine phosphate, followed by 250 mg given after 6 h, and 250 mg given once per day for the next 2 days. Before the initiation of chloroquine use, the patient had only a mild skin erythema in the irradiated area, which was consistent with the radiotherapy dose she had received. On day 3 of chloroquine treatment, she developed localised brisk bullous eruptions in the irradiated area, which peeled off rapidly in 6–7 h and developed into a patch of fulminant moist desquamation. The underlying subcutaneous tissues were healthy with no bleeding. The irradiated skin surrounding this patch developed severe erythema with characteristic, sharply demarcated borders (fi gure). Radiotherapy was withheld and the patient was managed conservatively with topical amniotic membrane and gentian violet application. 1 week later, her fever subsided and the moist desquamation had almost healed. Radiotherapy was restarted and completed uneventfully, with no recurrence of skin reactions. The patient was assessed 2 months after radiotherapy and showed substantial clinical improvement with restoration of motor power, resolution of cranial nerve palsies, and improved cerebellar signs. Repeat MRI revealed bulk and expanded pons with an ill-defi ned, heterogeneously hyperintense lesion on T2-weighted images. We saw patchy contrast enhancement that was suggestive of postradiotherapy change. A one-voxel MRI scan undertaken through the lesion showed a raised choline-to-creatine ratio that suggested residual disease. Comparison with the pretreatment MRI showed that the original lesion had reduced in size, but since the lesion in the follow-up scan was ill-defi ned, a formal comparison of sizes was not possible. The patient has since been put on regular follow-up. Although the radiosensitising activity of chloroquine has been well known on the basis of in vitro and animal studies, its eff ect in clinical practice is largely unknown. Chloroquine has been used as a radiosensitiser in small groups of patients with glioblastoma multiforme, who are given continuous treatment of low-dose chloroquine over an extended period during radiotherapy. Sotelo and colleagues did a randomised, double-blind, placebocontrolled trial of 30 patients with surgically confi rmed glioblastoma. Oral chloroquine at 150 mg/day or placebo was given for 12 months, beginning on day 5 after surgery. All patients received conventional chemotherapy and radiotherapy. Median survival after surgery was 24 months for chloroquine-treated patients and 11 months for controls. Although not signifi cantly diff erent, the rate of death in patients receiving chloroquine was about half of that in patients receiving placebo (p=0·139). Our patient had a rapid progressive moist desquamation with chloroquine, and the drug seemed to be the most probable cause. When reviewing the physics calculations and radiotherapy planning, we did not identify any error, Lancet Oncol 2006; 7: 608–09

Implication of PBP74/mortalin/GRP75 in the radio-adaptive response

Purpose : To investigate the relationship between expression of the human peptide-binding protein PBP74 and the occurrence of an adaptive response to ionizing radiation. Materials and methods : Human tumour cell lines HT29 and MCF-7 were transfected with a PBP74 or PBP74 antisense construct. For demonstration of an adaptive response, cells lines were irradiated with a conditioning dose of 0.25 Gy cobalt-60 γ-rays followed by a second dose of 4.0 Gy after an interval of 4.5 h. Response was measured in terms of clonogenic survival. Results : Transfection of a PBP74 plasmid caused transient overexpression of PBP74 mRNA in both cell lines. The optimal dose for the induction of PBP74 in the cell lines investigated was 0.1-0.25Gy and PBP74 induction occurred within 30 min of irradiation. For both cell lines, the adaptive response was repressed when cells were transfected with the anti-PBP plasmid. However, the converse, an enhancement of the adaptive response in cell lines transfected with the PBP74 construct, was seen only for HT29 cells under certain experimental conditions. Conclusions : The results support the view that while PBP74 is necessary to the adaptive response, it may not by itself be sufficient for the adaptive response to occur.

Thyroid dose in children undergoing prophylactic cranial irradiation

Purpose: To determine the radiation dose received by the thyroid gland as a result of prophylactic cranial irradiation (PCI) in childhood leukemia and the factors influencing that dose.Methods and Materials: The dose to the thyroid resulting from simulated cranial irradiation with parallel opposed lateral fields of an adult anthropomorphic (ART) phantom with both 6 MV X-rays and Cobalt-60 γ-rays was measured using thermoluminescent dosimeters (TLDs). The dependence of thyroid dose on the distance of the field from the thyroid and the proportions of thyroid dose from stray radiation (leakage, scatter from jaws, etc.) and tissue scattered radiation were measured. The effects of a shadow tray and shielding blocks were also determined. Calculation of thyroid dose using the Clarkson scatter integration method was performed for 6 MV X-rays to compare with the measured doses. In vivo thyroid dose estimates were made using TLD measurements for three children receiving PCI with 6 MV X-rays.Results: Using open, unshielded fields, the thyroid region of the phantom received 1.2–1.4% of the prescribed cranial dose for 6 MV X-rays and 1.5–1.7% for Cobalt-60. For both treatment units, stray radiation accounted for approximately two thirds of the thyroid dose and tissue scatter accounted for the remaining one third. The thyroid dose increased as the field moved closer to the thyroid, with an increasing proportion of the dose due to tissue scatter. Placement of a thyroid shielding block on a shadow tray reduced the thyroid dose by only 20% compared with the open, unshielded setup. Thyroid dose from 6 MV using open fields was affected by the orientation of the collimator. When the inferior field edge was defined by the lower jaw, the dose was reduced by 27% compared with the upper jaw. Good correlation of dose to the thyroid region was obtained between phantom measured doses, in vivo measured doses and calculation of dose using the Clarkson method.Conclusion: For PCI doses of 1800 or 2400 cGy in the adult phantom, the dose to the thyroid was 20–40 cGy (1–2%). For small children this could rise to approximately 5% of the prescribed dose, of which half was due to stray radiation. As the thyroid in children is very sensitive to radiation and the dose-response curve for thyroid tumor induction is linear, attempts to shield the thyroid during cranial irradiation are mandatory. Cobalt-60 units should not be used, as the thyroid dose was higher than using 6 MV X-rays. Collimator orientation and the use of shadow trays and shielding were important factors in determining thyroid dose.