Gabriele Hampel

Biosorption of copper by wine-relevant lactobacilli

Must and wine may be contaminated with elevated copper concentrations by the use of fungicides or in course of the vinification process. Hitherto only a few practicable and harmless procedures exist to reduce an excess of copper from must and wine. For this reason we investigated the biosorption of copper by eight wine-relevant Lactobacillus species. Both, living and heat-inactivated cells revealed a significant degree of Cu adsorption. It was shown that Cu binding correlated positively with an increasing pH value of the environment. The highest binding capacity of the tested lactic acid bacteria was found for L. buchneri DSM 20057 with a maximum of 46.17 μg Cu bound per mg cell in deionized water. In must, wine and grape juice Cu was removed less effective which is not solely attributed to low pH-values, but also to specific medium parameters such as intrinsic metal cations, organic acids or phenolic compounds. Nevertheless, about 0.5-1.0 μg Cu per ml could be removed from wine samples, which is sufficient enough to lower critical copper concentrations.

Towards a new measurement of the neutron electric dipole moment

The effort towards a new measurement of the neutron electric dipole moment (nEDM) at the Paul Scherrer Instituts (PSI) new high intensity source of ultracold neutrons (UCN) is described. The experimental technique relies on Ramseys 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.

Receptor-mediated uptake of boron-rich neuropeptide y analogues for boron neutron capture therapy.

Peptidic ligands selectively targeting distinct G protein‐coupled receptors that are highly expressed in tumor tissue represent a promising approach in drug delivery. Receptor‐preferring analogues of neuropeptide Y (NPY) bind and activate the human Y1 receptor subtype (hY1 receptor), which is found in 90 % of breast cancer tissue and in all breast‐cancer‐derived metastases. Herein, novel highly boron‐loaded Y1‐receptor‐preferring peptide analogues are described as smart shuttle systems for carbaboranes as 10B‐containing moieties. Various positions in the peptide were screened for their susceptibility to carbaborane modification, and the most promising positions were chosen to create a multi‐carbaborane peptide containing 30 boron atoms per peptide with excellent activation and internalization patterns at the hY1 receptor. Boron uptake studies by inductively coupled plasma mass spectrometry revealed successful uptake of the multi‐carbaborane peptide into hY1‐receptor‐expressing cells, exceeding the required amount of 109 boron atoms per cell. This result demonstrates that the NPY/hY receptor system can act as an effective transport system for boron‐containing moieties.

The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

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.

Forensic investigation of brick stones using instrumental neutron activation analysis (INAA), laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) and X-ray fluorescence analysis (XRF)

Brick stones collected from different production facilities were studied for their elemental compositions under forensic aspects using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), instrumental neutron activation analysis (INAA) and X-ray fluorescence analysis (XRF). The aim of these examinations was to assess the potential of these methods in forensic comparison analyses of brick stones. The accuracy of the analysis methods was evaluated using NIST standard reference materials (679, 98b and 97b). In order to compare the stones to each other, multivariate data analysis was used. The evaluation of the INAA results (based on the concentrations of V, Na, K, Sm, U, Sc, Fe, Co, Rb and Cs) using principal component analysis (PCA) and cluster analysis is presented as an example. The results derived from the different analytical methods are consistent. It was shown that elemental analysis using the described methods is a valuable tool for forensic examinations of brick stones.

Dose calculation in biological samples in a mixed neutron-gamma field at the TRIGA reactor of the University of Mainz

Abstract 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 7Li(n,α)3H-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.

Cellular uptake and in vitro antitumor efficacy of composite liposomes for neutron capture therapy

BackgroundNeutron capture therapy for glioblastoma has focused mainly on the use of 10B as neutron capture isotope. However, 157Gd 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.MethodsLiposomes 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 157Gd as neutron capturing agent was calculated via Monte Carlo simulations and set in relation to the respective cell survival.ResultsThe 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.ConclusionsLiposomal 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 157Gd 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.

Dosimetric feasibility study for an extracorporeal BNCT application on liver metastases at the TRIGA Mainz

This study investigates the dosimetric feasibility of Boron Neutron Capture Therapy (BNCT) of explanted livers in the thermal column of the research reactor in Mainz. The Monte Carlo code MCNP5 is used to calculate the biologically weighted dose for different ratios of the (10)B-concentration in tumour to normal liver tissue. The simulation results show that dosimetric goals are only partially met. To guarantee effective BNCT treatment the organ has to be better shielded from all gamma radiation.

Determination of Boron Concentration in Blood and Tissue Samples from Patients with Liver Metastases of Colorectal Carcinoma using Prompt Gamma Ray Activation Analysis (PGAA)

As part of the studies on Boron Neutron Capture Therapy at the University of Mainz, Germany, a clinical trial has been started in which, four patients suffering from liver metastases of colorectal carcinoma have been enrolled. Specimens of blood and healthy tissue samples taken from the patients were measured at the PGAA facilities at the HFR in Petten, The Netherlands, and at the FRM II in Munich, Germany. From the measured boron concentrations, pharmacokinetic curves and blood-to-tissue concentration ratios were produced.

Cubic boron nitride: A New prospective material for ultracold neutron application

Abstract At the ultracold neutron (UCN) source of the TRIGA research reactor in Mainz, we have measured for the first time the material optical wall-potential of cubic boron nitride. The measurements were performed with a time-of-flight (TOF) spectrometer. The samples investigated had a wall-potential of ( 305 ± 15 ) neV . This value is in good agreement with the result extracted from neutron reflectometry data and theoretical expectations. Because of its high critical velocity for UCN and its good dielectric characteristics, cubic boron nitride coatings (isotopically enriched) will be useful for a number of applications in UCN experiments.