Haut PDF Radiopharmaceutical dosimetry in targeted radionuclide therapy

Radiopharmaceutical dosimetry in targeted radionuclide therapy

Radiopharmaceutical dosimetry in targeted radionuclide therapy

administrated activity instead of absorbed dose. Therefore, more efforts must be undertaken to provide evidence to the physicians of a relevance of dosimetry for this treatment. In the case of hyperthyroidism, the case of the European Association of Nuclear Medicine (EANM) guidelines recommend prescribing different absorbed doses depending on the type of disease. Moreover, the EANM has dosimetry guidelines for both diseases targeting organs such as the thyroid itself and the bone marrow (Hänscheid et al., 2013; Hindorf et al., 2010; Lassmann et al., 2008). In these guidelines, how to calibrate the equipment, analyse patient data and how to estimate absorbed dose is described. Moreover, the International Atomic Energy Agency (IAEA) has created a report in which radiological protection recommendations are given to patients who are receiving these treatments (IAEA, 2009). To generate these recommendations, the administrated activity was the criteria used. Hence, isolation periods from relatives, co-workers, time to sleep alone and visits from children are defined for patients who underwent thyroid cancer (for ablation or recurrence) and hyperthyroidism treatments. This comprehensive report also considers how to proceed with pregnant patients (or potentially pregnant), under breast-feeding and even patient death, thus, how to manage radioactive bodies and how-to carry-on an autopsy, are topics also considered. On the other hand, the United States Nuclear Regulatory Commission (USNRC) (Howe et al., 2008), in the appendix U, considering biokinetics of the 131 I into the patient and try to personalize
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Multi-scale dosimetry for targeted radionuclide therapy optimisation

Multi-scale dosimetry for targeted radionuclide therapy optimisation

defined, and the absorbed dose to the bladder, the bladder wall and the uterus is scored. The source spatial distribution in the LR–SS model coincided with the bladder voxels. For both high resolution models, the source optimisation procedure described in section 5.2.3 was implemented in order to achieve reasonable simulation times for the HR–SS model. For this proof of principle example two different radionuclides sources ( 90 Y and 131 I) were implemented as they provide beta emissions of very different endpoint energies (2.28 MeV for 90 Y and 606.31 keV for 131 I ) well covering the range of beta energies typically used in TRT. These sources also offer the possibility of comparing the dosimetric impact of a pure β-emitter as 90 Y, and a beta/gamma emitter as 131 I (main gamma emission at 364.49 keV). Sources were generated using the General Particle Source module in Geant4 and the G4Ion class (Marcatili S. et al. 2013). For the three geometries the same physics list (G4EmStandardPhysics option4 ) was used, implementing Livermore models (Chauvie et al. 2004) for the simulation of electromagnetic interactions down to 250 eV. These models have already been validated by several authors for Targeted Radionuclide Therapy applications (Amato et al. 2013, Mauxion et al. 2013, Papadimitroulas et al. 2012, Maigne et al. 2011), and they are based on the evaluated tables from LLNL (Lawrence Livermore National Laboratory): EPDL97 (Cullen et al. 1997), EEDL (Perkins et al. 1991a) and EADL (Perkins et al. 1991b). Specific cuts, consistent with the voxel size implemented have been applied. The voxel statistical uncertainty (standard deviation of the mean) was calculated at simulation time by considering the actual number of particles releasing their energy in the voxel (N v ) and it scales as 1/  N v (N v − 1) (Visvikis et al. 2006).
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Impact of Mouse Model on Pre-Clinical Dosimetry in Targeted Radionuclide Therapy

Impact of Mouse Model on Pre-Clinical Dosimetry in Targeted Radionuclide Therapy

More recently, quantitative imaging has paved the way for longitudinal studies [16], allowing the pharmacokinetics to be determined for each individual animal. The accuracy of such an approach remains to be ascertained. Operational issues such as the ability to sequentially anesthetize the same animal safely, or to fuse images obtained at different time points with accuracy on par with the spatial resolution of the imaging devices have to be addressed [17]. The radiation burden resulting from the sequential use of microCT is generally not lethal, but the absorbed dose levels may be sufficient to induce deterministic effects that could confound the biological outcome of the experiment [18]. Still, it must be considered that animal-specific pharmacokinetics are or will be available within the near future from micro imaging devices (micro-PET/CT or micro-SPECT/CT). In that context, the relevance of model-based dosimetry may have to be reconsidered: If cumulated activities can be obtained for a given animal, then on principle the absorbed dose should be determined for the animal itself rather than for a model, unless it can be proven that using a model does not impact the dosimetric results markedly.
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Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy

Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy

ICF15002 was firstly selected as a good candidate from a series of arylcarboxamide derivatives on the basis of its radiochemical properties and physicochemical properties [21,22] . This preclinical work highlights the interest of ICF15002, when radiolabeled either with fluorine-18 or iodine-131, for a theranostic management of melanoma. First of all, biodistribution of [ 18 F]ICF15002 was characterized in murine and human melanoma models by both in vivo PET imaging and ex vivo biodistributions. As expected, biodistribution studies in melanoma-bearing mice demonstrated an early and high tumor accumulation of [ 18 F]ICF15002, as early as 30 minutes p.i., correlated to pigmentation (r 2 = 0.98) and leading to high and durable tumor-to-muscle ratios (12.12 ± 1.74 for B16BL6 and 4.23 ± 1.11 for SK-MEL-3 at 1 hour p.i.). It should be mentioned that [ 18 F]ICF15002 uptake in the eyes of the animals differs between the two mouse models showing specificity of targeting: a high uptake was observed in the highly pigmented eyes of C57BL/6J mice, whereas a low pattern was observed in the amelanotic eyes of nude mice. This is consistent with the ability of ICF15002 to bind to melanin in vivo. The specific affinity of ICF15002 for melanin was confirmed at the cellular level by SIMS analysis of pulmonary melanoma micronodules: a colocalization of the iodine signal of ICF15002 with that of melanin was clearly evidenced in tumor cell melanosomes.
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Implementation of patient dosimetry in the clinical practice after targeted radiotherapy using [177Lu-[DOTA0, Tyr3]-octreotate

Implementation of patient dosimetry in the clinical practice after targeted radiotherapy using [177Lu-[DOTA0, Tyr3]-octreotate

In PRRT with 177 Lu, the important inter-patient varia- tions in peptide pharmacokinetics require treatment individualization by tailoring the number of cycles or the administered activity [ 11 ]. In this context, therapy plan- ning based on the maximum tolerable absorbed dose to non-target organs (“as high as safely attainable”, AHASA approach) [ 12 ] could be considered, instead of the “as low as reasonably achievable” (ALARA) approach (i.e., the dose to non-target tissues should be reasonably low). However, currently, a fixed activity of 7.4 GBq per cycle, as described in the NETTER-1 trial, is usually adminis- tered. Hence, personalized dosimetry is often performed mainly to ensure safety and evaluate the absorbed dose to the tumor rather than to optimize the administered activity and to assess the dose-response relationship.
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A review of the use and potential of the GATE Monte Carlo simulation code for radiation therapy and dosimetry applications

A review of the use and potential of the GATE Monte Carlo simulation code for radiation therapy and dosimetry applications

izing radiations. 2 In radiation therapy (RT), treatment plan- ning requires an accurate assessment of the absorbed dose distribution throughout the organs and tissues of interest. This is true for a large variety of RT approaches (e.g., us- ing photons, electrons, protons, carbon beams, radioisotopes) with different delivery conditions (broad beam, pencil beam, scanning, rotational, brachytherapy, and targeted radionuclide therapy). In diagnostic imaging applications involving ioniz- ing radiation, such as computed tomography (CT), positron emission tomography (PET), or single photon emission to- mography (SPECT), the assessment of the absorbed dose is important to better analyze the risk-benefit of the pro- cedure. Imaging and therapy are increasingly tied together: cone-beam or portal imaging are associated with conventional linac RT, CT acquisitions are performed during tomother- apy, radiographs pairs are acquired during Cyberknife treat- ments, and new imaging systems are developed for treatment monitoring in hadrontherapy, such as hadron-PET, 3 , 4 prompt-
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en fr Development of a new anti-cancer agent for targeted radionuclide therapy : ß- radiolabeled RAFT-RGD. Le RAFT-RGD radiomarqué avec un émetteur °- comme nouvel agent de radiothérapie interne vectorisée

26  Les effets particuliers des faibles doses (inférieures à 0,2 Gy) o Effet de proximité La radiosensibilité d’une cellule peut être augmentée ou diminuée du fait de ses interactions avec les cellules voisines, soit par les jonctions, soit par le milieu extracellulaire. On regroupe sous le terme d’effets de proximité (« bystander effect ») les effets d’une radioexposition sur les cellules non irradiées. Les mécanismes de cet effet de proximité reposent sur la communication intercellulaire à travers les jonctions gap et la sécrétion de facteurs solubles (comme TGF et NO) (Prise, Nat Rev Cancer 2009). La signalisation mitochondriale joue également un rôle central dans ce phénomène (Hei, Curr Mol Pharmacol 2011). Cet effet de proximité contribue à l'augmentation de la mort dans les cellules tumorales (Kassis, Hum Exp Toxicol 2004). Cet effet est prédominant aux faibles doses d'irradiation inférieures à 0,2 Gy (Prise, Radiat Prot Dosimetry 2003) et atteint un plateau à partir de 1 Gy (Prise, Nat Rev Cancer 2009).
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Synthesis of lutetium-carrying oligonucleotides for targeted cancer therapy and imaging

Synthesis of lutetium-carrying oligonucleotides for targeted cancer therapy and imaging

In cancer therapy there is need for targeted treatment that kills tumour cells selectively while minimizing damage to healthy cells. In this regard, specific targeting of tumours through radiopharmaceuticals is increasingly considered as a promising strategy in oncology. Radiopharmaceuticals consist of a radionuclide coupled to a vector that specifically targets cancer-related molecules. The radionuclide, for example lutetium-177, will be used to visualize and/or kill the tumour cells through ionizing irradiation.
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Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases

Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases

Thermo Fisher Scientific, UK; pH 7.4), quenched with 1% hydrogen peroxide (Sigma Aldrich, UK) in methanol and blocked in 10% normal goat serum for VCAM-1 expression or normal horse serum for CD31. Primary antibody was incubated overnight at 4° C, using 1:250 dilution for VCAM-1 (rat anti-mouse, Cambridge Bioscience, 1510-14) or 1:100 dilution for CD31 (goat anti-mouse, Bio-Techne R&D, AF3628). Samples were then incubated for 1 h at room temperature using a biotinylated goat anti-rat (1:100, vectorlabs, CA, USA) or biotinylated horse anti-goat secondary antibody (1:200, vectorlabs). After amplification using the ABC reaction, staining was detected using standard DAB/hydrogen reaction. Sections were counterstained using cresyl violet and mounted using DPX mounting solution (Thermo Fisher Scientific, UK). Slides were scanned using an Aperio brightfield scanner (Leica Biosystems) and analysed using ImageScope®. Histologic sections of mouse brain parenchyma were used to measure the diameter of CD31-stained blood vessels and the depth of cancer cell infiltration into brain tissue. These data were used to generate a geometric model for MC simulation that reflected the dimensions of brain metastases at 21 days following intracardiac injection in the MDA231BR model.
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Introduction to Radiobiology of Targeted Radionuclide Therapy

Introduction to Radiobiology of Targeted Radionuclide Therapy

Bystander effects include mutations, clastogenic effects, cell death, apoptosis, and cell transformation ( 6 ). They mainly occur after low dose (<1 Gy) or low dose-rate irradiation, although they have been observed in EBRT also after high absorbed dose (10 Gy). They involve signaling from irradiated cells toward non- irradiated cells. Specifically, stress mediators are transmitted to bystander cells by cell–cell interactions through gap junction inter- cellular communication (GJIC) when cells are in contact and the molecules are small (<1500 Da) (Figure 1),or by the release of sol- uble damage/stress signals that may have distant biological effects (abscopal effect) ( 6 , 48 – 50 ). These mediators can be ROS/NO, cytokines (interleukin 8, interleukin 6, tumor necrosis factor, and interleukin-33), Ca 2+ , or extracellular DNA (ecDNA). They are produced by irradiated cells and are released in the extracellular environment ( 39 ), thus inducing oxidative stress in neighbor- ing cells/tissues. However, they can be active also within the cell in an autocrine way. They can also activate immune cells (for instance, macrophages and T lymphocytes) that, in turn, release cytokines, leading to iNOS induction, and NO formation ( 51 ). Therefore, the inflammatory and radiation responses share com- mon mechanisms to promote and perpetuate a harmful inflamma- tory/oxidative stress environment. This new paradigm also high- lights the role of the tumor (or healthy tissue) microenvironment
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Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy

Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy

TALEN vector pair 33 designed to introduce a double-strand break adjacent to the R14del mutation of the PLN and validated its efficiency by the surveyor assay 34 (Supplementary Fig. 3). Patient- derived iPSCs were co-transfected with a PLN-specific TALEN pair together with the gene correction matrix (Fig. 2a). We obtained two isogenic iPSC clones, designated L2GC1 and L2GC2, which differ only in the R14del mutation with the parent clone L2. The corrected clones were expanded and the correction of the R14del mutation was confirmed by Sanger sequencing (Fig. 2b and Supplementary Fig. 4). Similarly to the parental line, the TALEN-edited isogenic iPSCs clones were characterized and confirmed to be pluripotent and karyotypically normal (Supplementary Fig. 5). We differentiated the corrected clones into CMs, and determined that the targeted gene correction did not alter the gene expression level of PLN and appropriate expression of the ‘TALEN-corrected’ allele was confirmed in the isogenic CMs of both clones by pyrosequencing (Fig. 2c). In addition, we performed whole- exome sequencing and bioinformatics analyses to assess off-target mutagenesis. Consistent with recent reports 35–37 , exome sequencing of the parental and TALEN-corrected iPSCs showed that off-target mutations attributable to the TALENs were very rare (Supplementary Table 1). Next we sought to determine whether the genetic correction of the R14del mutation resulted in functional phenotypic correction. We observed that TALEN- corrected CMs displayed a normal Ca 2 þ cycling phenotype (Fig. 3a–c), and a significantly lower resting diastolic Ca 2 þ levels compared to CMs derived from the the parent line
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First in-human radiation dosimetry of 68Ga-NODAGA-RGDyK

First in-human radiation dosimetry of 68Ga-NODAGA-RGDyK

As recommended by the MIRD pamphlet 16 for a three-data point study [26], a mono-exponential fit ex- tended to infinite beyond the last measured data point was used to derive time-integrated activity coefficients (TIAC) in each selected organ. The goodness of fit for each organ was expressed by the R 2 metric. Organ resi- dence times were obtained by dividing TIAC for the ad- ministered 68 Ga total activity. For each patient, two red marrow VOIs were drawn, the first in the heads of both femora and the second in the lumbar vertebrae L3–L4. The total number of disintegration which occurred in the red marrow was obtained by averaging the number of disintegration per unit of mass of these two regions and then multiplying this value by the red marrow mass of the OLINDA adult male reference phantom [27]. This methodology is an extension to 3D images of the method presented by Ferrer et al. [28]. The calculation performed in two separate bone marrow regions, the lumbar vertebrae (L3–L4) and the head of femora aimed at reducing quantitative bias due to heterogeneity in red marrow uptake [29]. Since no relevant heterogeneities of activity distribution were observed in the colon tract, the total number of disintegrations in this organ was parti- tioned to its components (upper large intestine, lower large intestine) proportionally to their respective masses of the OLINDA male reference phantom. Organ resi- dence times were used in input to the OLINDA/EXM (Organ Level INternal Dose Assessment/EXponential Modeling) code [30]. OLINDA/EXM provided organ absorbed doses and effective dose (ED) per absorbed ac- tivity in μGy/MBq and μSv/MBq, respectively, using the ICRP60 tissue weighting factors [31]. The ED was also re-evaluated manually from organ equivalent doses adopting the tissue weighting factors recommended by
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Polymeric Encapsulation of a Ruthenium Polypyridine Complex for Tumor Targeted One- and Two-Photon Photodynamic Therapy

Polymeric Encapsulation of a Ruthenium Polypyridine Complex for Tumor Targeted One- and Two-Photon Photodynamic Therapy

protein, receptor targeting moiety or an antibody, is used to transport the therapeutic molecule. 15-17 A large variety of transition metal complexes have been successfully coupled to peptides resulting in increased receptor selectivity. 18-20 As examples for Ru(II) polypyridine complexes, the conjugation to the peptide hormone somatostatin showed a 100-fold increased selectivity for somatostatin receptor-expressing cells relative to the free PS. 21 The covalent conjugation of a Ru(II) polypyridine complex to the human gastrin-releasing peptide receptor or a nuclear localization signal peptide, resulted in a higher uptake of the conjugate in receptor- expressing cells in comparison with the complex itself. 22 The conjugation of the receptor binding peptides Arg-Gly-Asp (RGD) and octreotide, which are overexpressed in various kinds of cancers, to a Ru(II) arene complex were also reported. 23 Capitalizing on these results, a conjugate consisting of a RGD peptide and a Ru(II) polypyridine was recently reported as a selective prodrug. 24 As a different type of delivery system, the conjugation of a Ru(II) polypyridine complex to an epidermal growth factor receptor specific nanobody was shown to have high selectivity for this receptor. 25 Recently the conjugation of a Ru(II) polypyridine to the blood plasma protein serum albumin as a mitochondria selective delivery system was reported. 26 On the contrary, when a passive targeting approach is taken, the nature of the tumour, which includes its leaky, highly permeable vasculature and poor lymphatic tissue characteristics, is used to selectively bring a drug to its target. This passive targeting approach could be achieved by oil dispersions, loading onto nanoparticles, encapsulation in polymeric particles or liposomes 27-29 , although this concept is currently controversial discussed. 30 As examples, selenium 31-33 , silver 34 , gold 35-37 and silicon 38-40 nanoparticles as well as upconverting 41-43 nanoparticles were successfully loaded with Ru(II) polypyridine complexes, forming a drug delivery vehicle. Further, the physical encapsulation of Ru(II) polypyridine complexes into polymeric particles 44-49 , micelles 50-52 , dendrimers 53 or liposomes 54-55 was reported. Despite these efforts, the majority of the previously mentioned transport systems are associated with a poor water solubility, tedious preparation, high price or a diminished therapeutic effect. To overcome these limitations, there is an urgent need for a simple, water-soluble, cheap and selective delivery system.
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Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile

Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile

resistance in LPS. Global dose effect confirmed the awaited efficiency of AMG 900 and is encouraging for conducting animal experiments to confirm the results. However, these data also revealed heterogeneity regarding in vitro drug response. In some cell-lines, the high response at low doses, compared to doxorubicin, is a good indicator to test AMG 900 as monotherapy. Moreover, similar efficiency was observed in other STS cell-lines when combined with doxorubicin. This should help to decrease doxorubicin doses thus reducing adverse effects, especially in the elderly, or to open new lines of treatment in refractory tumours. These findings may lead to investigate the criteria linked to the response rate, which could help to decide the best regimen for patients. Molecular characterization of each tumour could become mandatory before treatment, because the specific genetic heterogeneity of sarcomas appears likely linked to drug efficiency.
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Multichannel OSL dosimetry for dose verification in radiotherapy

Multichannel OSL dosimetry for dose verification in radiotherapy

The first generation system (OSL I) relied on Alkaline-Earth Sulphide (AES) materials, stimulated by infrared laser light. The OSL is in the red part of the visible spectrum. The corresponding absorption in silica fibres is ~10 dB/km enabling remote operation up to several hundreds of meters. The OSL I system did not provide tissue-equivalent dose measurement and its dose range was [1 mGy, 10 Gy]. It was well suited to dismantling applications because of its unique feature of remote dose monitoring inside narrow pipes and tanks and was widely used at CEA and AREVA NC (Marcoule, France). The second generation system (OSL II) relies on alumina crystals, stimulated by a green laser light. The OSL is in the blue part of the visible spectrum. The corresponding absorption in silica fibres is ~80 dB/km and the practical fibre length is thus restricted to several tens of meters. The OSL II system was investigated for radiation protection applications that require a limit in dose detection better than some µGy and may involve a compensation technique to fit the tissue response.
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The IRS Fricke dosimetry system

The IRS Fricke dosimetry system

move the sample transport outwards. This can be easily seen when looking at the sloped part of the scan. A zoomed-in version of the downward slope of the 303 nm scan before modifications is shown in Figure 3. It shows that for approximately 10 steps of the motor there is no change in % transmittance, so the sample holder is not moving. After 10 steps the sample holder jumps 10 steps forward, and then the cycle is repeated. These data suggest that after 10 steps of the rotor there is enough potential energy stored in the spring that when the motor tries to move the sample transport accessory by 1 step, the torque produced combined with the energy stored in the spring results in forward motion of the sample holder (approximately 11 steps). Putting a Teflon washer on the motor shaft and clipping it in place rectified this problem. This arrangement ensures that there is no horizontal play in the rotor movement. The trade off is that it introduces extra friction when the rotor turns, because now it not only has to move the compartment but also the washer that is in contact with the motor wall. The increased torque allows the motor to handle the load. When all the modifications were completed, new scans were done of % transmission vs. number of steps. Figure 4 shows one of these plots at 303 nm. Figure 5 is a zoomed-in version of 303 nm data from Figure 4. There is no periodic motion observed in the movement of the sample transport. The one step at-a-time motion is very reliable.
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Radionuclide distribution in tidal flat sediments of the Westerschelde estuary

Radionuclide distribution in tidal flat sediments of the Westerschelde estuary

the Molenplaat stations, based on organic carbon content and sedimentation rates of the sediment cores, vary between 10 and 105 gC m" 2 y\ which is about 30 - 40 % of the total yea[r]

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Fiber-Coupled, Time-Gated Al$_2$O$_3$:C Radioluminescence Dosimetry Technique and Algorithm for Radiation Therapy With LINACs

Fiber-Coupled, Time-Gated Al$_2$O$_3$:C Radioluminescence Dosimetry Technique and Algorithm for Radiation Therapy With LINACs

 Abstract— An original algorithm for real-time In Vivo Dosimetry (IVD) based on Radioluminescence (RL) of dosimetric- grade Al2O3:C crystals is described and demonstrated in reference conditions with 12-MV photon beams from a Saturne 43 linear accelerator (LINAC), simulating External Beam Radiation Therapy (EBRT) treatments. During the course of irradiation, a portion of electrons is trapped within the Al2O3:C crystal while another portion recombines and generates RL, recorded on-line using an optical fiber. The RL sensitivity is dose- dependent and increases in accordance with the concentration of trapped electrons. Once irradiation is completed, the Al2O3:C crystal is reset by laser light (reusable) and the resultant OSL (Optically Stimulated Luminescence) is also collected back by the remote RL-OSL reader and finally integrated to yield the absorbed dose. During irradiation, scintillation and Cerenkov lights generated within the optical fiber ("stem effect") are removed by a time-discrimination method involving a discriminating unit and a fiber-coupled BGO scintillator placed in the irradiation room, next to the LINAC. The RL signals were then calibrated with respect to reference dose and dose rate data using an ionization chamber (IC). The algorithm relies upon the integral of the RL and provides the accumulated dose (useful to the medical physicist) at any time during irradiation, the dose rate being derived afterwards. It is tested with both step and arbitrary dose rate profiles, manually operated from the LINAC control desk. The doses measured by RL and OSL are both compared to reference doses and deviations are about ± 2 % and ± 1 % respectively, thus demonstrating the reliability of the algorithm for arbitrary profiles and wide range of dose rates. Although the calculation was done off-line, it is amenable to real- time processing during irradiation.
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Targeted photoredox catalysis in cancer cells

Targeted photoredox catalysis in cancer cells

8.9. Intracellular ATP concentration 1×10 4 cells were seeded per well in 96-well plates (Costar) at 310 K in a 5% CO 2 /95% air incubator (Thermo) for 24 h. The cells were treated with complex 1 (2 light IC 50 , normoxia 3 M, hypoxia 5 M) for 2 h. After this, supernatants were removed by suction and each well was washed with 1 PBS. For light treatment, the cells were then irradiated in phenol red-free cell culture medium under normoxia (20% O 2 , 465 nm, light dose 8.9 J/cm 2 ). The cells were allowed to recover for a further 6 h in an incubator at 310 K. Then CellTiter-Glo reagent (Promega) was added to each well, and then the plate was shaken for 2 min, and incubated for 10 min at ambient temperature. The luminescence was recorded using a microplate reader (GloMax-Multi Microplate Multimode Reader). The cellular ATP concentrations were determined as duplicates of triplicates, as part of two independent experiments, and the standard deviations were calculated. Statistical significances were determined using Welch’s t-test.
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Effects of radionuclide contamination on leaf litter decomposition in the Chernobyl exclusion zone

Effects of radionuclide contamination on leaf litter decomposition in the Chernobyl exclusion zone

and DNA damage decreased in wild birds exposed to chronic low-dose radiation at CEZ. They concluded that birds may adapt to chronic expo- sure to ionizing radiation with a hormetic response. (ii) Because we used leaf litter material from uncontaminated control sites, decom- posers may have preferred this exogenous leaf litter material over local leaf litter which may have a lower overall quality. Leaf litter quality is a major factor affecting decomposer communities (e.g. Melillo et al., 1982; Cornwell et al., 2008). Similar to the negative effect of heavy metal pollution on leaf litter quality and subsequently reduced decom- position rates (Killham and Wainwright, 1981; Berg et al., 1991; McEnroe and Helmisaari, 2001; Johnson and Hale, 2004), exposure to radionuclides may negatively affect leaf litter quality. Having the choice between the locally produced leaf litter material and the uncontaminat- ed leaf litter of potentially higher quality, decomposer organisms may have shown a preference for the latter. Such a preference effect would be expected to increase with increasing radioactive exposure, i.e. de- creasing local litter quality, which is in line with our observations. To test this hypothesis, future studies should assess quality differences along contamination gradients and compare decomposition between locally produced and exogenous leaf litter.
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