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Background: Neutron capture therapy for glioblastoma has focused mainly on the use of (10)B as neutron capture isotope. However, (157)Gd offers several advantages over boron, such as higher cross section for thermal neutrons and the possibility to perform magnetic resonance imaging during neutron irradiation, thereby combining therapy and diagnostics. We have developed different liposomal formulations of gadolinium-DTPA (Magnevist®) for application in neutron capture therapy of glioblastoma. The formulations were characterized physicochemically and tested in vitro in a glioma cell model for their effectiveness., Methods: Liposomes entrapping gadolinium-DTPA as neutron capture agent were manufactured via lipid/film-extrusion method and characterized with regard to size, entrapment efficiency and in vitro release. For neutron irradiation, F98 and LN229 glioma cells were incubated with the newly developed liposomes and subsequently irradiated at the thermal column of the TRIGA reactor in Mainz. The dose rate derived from neutron irradiation with (157)Gd as neutron capturing agent was calculated via Monte Carlo simulations and set in relation to the respective cell survival., Results: The liposomal Gd-DTPA reduced cell survival of F98 and LN229 cells significantly. Differences in liposomal composition of the formulations led to distinctly different outcome in cell survival. The amount of cellular Gd was not at all times proportional to cell survival, indicating that intracellular deposition of formulated Gd has a major influence on cell survival. The majority of the dose contribution arises from photon cross irradiation compared to a very small Gd-related dose., Conclusions: Liposomal gadolinium formulations represent a promising approach for neutron capture therapy of glioblastoma cells. The liposome composition determines the uptake and the survival of cells following radiation, presumably due to different uptake pathways of liposomes and intracellular deposition of gadolinium-DTPA. Due to the small range of the Auger and conversion electrons produced in (157)Gd capture, the proximity of Gd-atoms to cellular DNA is a crucial factor for infliction of lethal damage. Furthermore, Gd-containing liposomes may be used as MRI contrast agents for diagnostic purposes and surveillance of tumor targeting, thus enabling a theranostic approach for tumor therapy.

Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed., Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a (60)Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes fluka and mcnp. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen & Olsen alanine response model., Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields., Conclusions: The alanine detector can be used without difficulty in neutron fields. The response has been understood with the model used which includes the relative effectiveness. Results and the corresponding discussion lead to the conclusion that application in neutron fields for medical purpose is limited by its sensitivity but that it is a useful tool as supplement to other detectors and verification of neutron source descriptions.

Unlabelled: Boron Neutron Capture Therapy for liver malignancies is being investigated at the University of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may be suitable for measurements in mixed neutron and gamma fields., Material and Methods: Two experiments have been carried out in the thermal column of the TRIGA Mark II reactor at the University of Mainz. Alanine dosimeters have been irradiated in a phantom and in liver tissue., Results: For the interpretation and prediction of the dose for each pellet, beside the results of the measurements, calculations with the Monte Carlo code FLUKA are presented here. For the phantom, as well as for the liver tissue, the measured and calculated dose and flux values are in good agreement., Discussion: Alanine dosimeters, in combination with flux measurements and Monte Carlo calculations with FLUKA, suggest that it is possible to establish a system for monitoring the dose in a mixed neutron and gamma field for BNCT and other applications in radiotherapy.

To establish Boron Neutron Capture Therapy (BNCT) for non-resectable liver metastases and for in vitro experiments at the TRIGA Mark II reactor at the University of Mainz, Germany, it is necessary to have a reliable dose monitoring system. The in vitro experiments are used to determine the relative biological effectiveness (RBE) of liver and cancer cells in our mixed neutron and gamma field. We work with alanine detectors in combination with Monte Carlo simulations, where we can measure and characterize the dose. To verify our calculations we perform neutron flux measurements using gold foil activation and pin-diodes. Material and methods. When L-α-alanine is irradiated with ionizing radiation, it forms a stable radical which can be detected by electron spin resonance (ESR) spectroscopy. The value of the ESR signal correlates to the amount of absorbed dose. The dose for each pellet is calculated using FLUKA, a multipurpose Monte Carlo transport code. The pin-diode is augmented by a lithium fluoride foil. This foil converts the neutrons into alpha and tritium particles which are products of the (7)Li(n,α)(3)H-reaction. These particles are detected by the diode and their amount correlates to the neutron fluence directly. Results and discussion. Gold foil activation and the pin-diode are reliable fluence measurement systems for the TRIGA reactor, Mainz. Alanine dosimetry of the photon field and charged particle field from secondary reactions can in principle be carried out in combination with MC-calculations for mixed radiation fields and the Hansen & Olsen alanine detector response model. With the acquired data about the background dose and charged particle spectrum, and with the acquired information of the neutron flux, we are capable of calculating the dose to the tissue. Conclusion. Monte Carlo simulation of the mixed neutron and gamma field of the TRIGA Mainz is possible in order to characterize the neutron behavior in the thermal column. Currently we also speculate on sensitizing alanine to thermal neutrons by adding boron compounds.

We have determined for the first time the velocity distribution of neutrons from a solid 2H2 ultracold neutron (UCN) source. The spectrum rises sharply above 4.5m/s and has a maximum around 7m/s after transport in an 8m long guide. The number of neutrons in the UCN velocity range (< 7m/s) may be increased by a factor of two by placing the experiment 1m above the UCN source level. [ABSTRACT FROM AUTHOR]

Abstract: The effort towards a new measurement of the neutron electric dipole moment (nEDM) at the Paul Scherrer Institut''s (PSI) new high intensity source of ultracold neutrons (UCN) is described. The experimental technique relies on Ramsey''s method of separated oscillatory fields, using UCN in vacuum with the apparatus at ambient temperature. In the first phase, R&D towards the upgrade of the RAL/Sussex/ILL apparatus is being performed at the Institut Laue-Langevin (ILL). In the second phase the apparatus, moved from ILL to PSI, will allow an improvement in experimental sensitivity by a factor of 5. In the third phase, a new spectrometer should gain another order of magnitude in sensitivity. The improvements will be mainly due to (1) much higher UCN intensity, (2) improved magnetometry and magnetic field control, and (3) a double chamber configuration with opposite electric field directions. [Copyright &y& Elsevier]

Abstract: Photon dose measurements in radiation fields having the proper characteristics for boron neutron capture therapy (BNCT) present several troubles. The thermal neutron flux is very high and produces a significant contribution to the response of most dosimeters. The consistency of photon dose measurements with :Tm and LiF:Mg, Ti thermoluminescent dosimeters has been studied. A method is described for obtaining the gamma dose with TLD-700 and some results are presented to test its reliability. [Copyright &y& Elsevier]

Abstract: Strong fields of thermal and epithermal neutrons as used for Boron Neutron Capture Therapy (BNCT) show a relatively small gamma dose. However, for accurate dose estimation, both the neutron as well as the gamma component has to be considered. Different approaches have been studied with various thermoluminescence detectors (TLDs). As a result, CaF2:Tm detectors (TLD-300) are attributed to be most insensitive to thermal neutrons but not tissue-equivalent. In this paper we focus on the measurement of the gamma dose with TLD-300 in mixed irradiation fields. To overcome the disadvantage of being not tissue-equivalent, a study on energy compensation filters was performed. The paper comprises also calibrations of TLD-300 using energy compensation filters at the PTB-reference field for thermal neutrons, and first test experiments at the TRIGA Mainz including simulations. [Copyright &y& Elsevier]

Abstract: We describe the status of the new measurement of the neutron electric dipole moment (nEDM) to be performed at the strong source of ultra-cold neutrons at the Paul Scherrer Institut. The experimental technique is based on Ramsey''s method of separated oscillatory fields, applied to UCN stored in vacuum in a chamber at room temperature. Our approach is performed in three phases: in phase one, new components have been developed and tested at the Institut Laue-Langevin. Phase two is being performed at PSI, where the apparatus was moved in 2009. Here, together with the optimization of the magnetic environment, the prospective UCN density of ∼ 100 cm-3 should enable an improvement of the currently best limit by a factor of five within two years of data taking. In the third phase, a new spectrometer will then gain another order of magnitude in sensitivity. The improvements will be mainly due to (1) much higher UCN intensity, (2) improved magnetometry and magnetic field control, and (3) a double chamber configuration with opposite electric field directions. [Copyright &y& Elsevier]