The Mobile Analyzer of Radioactive Gases OuTflows (MARGOT): A promising environmental xenon radionuclides detection system.

An ultra-compact and unshielded spectrometer for analysis of atmospheric xenon radionuclides has been developed: the MARGOT system. This system works at ambient temperature and high pressure, and has a 54.3 cm3 inner active volume. Atmospheric xenon radionuclide activities are determined with the electron-photon coincidence technique using both NaI(Tl) detectors and large pixellized Si-PIN detectors. The MARGOT system integrates an enhanced version of the PIPSBox™, Geant4 simulation and first calibration results are discussed.

Introducing the MARGOT prototype: An ultra-compact and mobile gas detection system for nuclear explosion monitoring.

An ultra-compact and unshielded spectrometer for analysis of atmospheric radioxenons has been developed. This system works at ambient temperature and has a 58 cm3 inner active volume. Atmospheric radioxenons activities are determined with electron/photon coincidence technique using both NaI(Tl) detector and large pixellized Si-PIN detector. The performances of the detection system without shielding in terms of Minimal Detectable Activities are below 65 mBq for a 12 h acquisition, for all radioxenons of interest. An enhanced version of the prototype presented here is already under development: the Mobile Analyzer for Radioactive Gases OuTflows (MARGOT) system.

Low-level laboratory measurement of xenon radionuclides: Electron-photon versus photon measurements.

Radioactive xenon (mainly 131mXe, 133Xe, 133mXe and 135Xe) are tracked as markers of nuclear weapons testing. The CEA has developed the PIPSBox, a measurement cell able to detect electrons emitted by xenon nuclides. Combined with an ultra-low background γ spectrometer, electron detection capacities allow reaching minimum detectable activities (MDA) for a 3-day long measurement of about 0.5mBq for the four xenon radionuclides. Compared to a classical measurement cell, MDAs are improved by a factor of 2-4.

SPALAX NG: A breakthrough in radioxenon field measurement.

Lessons-learned from 10 years of noble gas stations operation and dedicated R&D allowed the design of a New Generation of station. In order to produce 60m3 air equivalent Xenon samples every 8h, it implements: (i) larger sampler unit for Xenon extraction (2 compressors and 8 nitrogen membranes), (ii) new noble gas adsorbent (Ag@ZSM5), (iii) hardened components and (iv) new high resolution coincidence low background spectrometer (HPGe/PIPSBox). Station expected radioxenon sensitivity is lower than 0.3mBq/m3.

Ground surface ultralow background spectrometer: Active shielding improvements and coincidence measurements for the Gamma3 spectrometer.

The ultralow background versatile spectrometer GAMMA3 has been optimized with the following shielding improvements: (i) optimized nitrogen injection flux of 300Lh-1, and (ii) cosmic veto configuration with 9 scintillating plates. These improvements allow a reduction of 39% of the normalized integral background count rate down to 2.7±0.2min-1kgGe-1 (40-2500keV energy range). Minimum Detectable Activities when performing direct γ-ray spectrometry or γ-γ coincidence spectrometry are compared.

Spalax™ new generation: A sensitive and selective noble gas system for nuclear explosion monitoring.

In the context of the verification regime of the Comprehensive nuclear Test ban Treaty (CTBT), CEA is developing a new generation (NG) of SPALAX™ system for atmospheric radioxenon monitoring. These systems are able to extract more than 6cm(3) of pure xenon from air samples each 12h and to measure the four relevant xenon radioactive isotopes using a high resolution detection system operating in electron-photon coincidence mode. This paper presents the performances of the SPALAX™ NG prototype in operation at Bruyères-le-Châtel CEA centre, integrating the most recent CEA developments. It especially focuses on an innovative detection system made up of a gas cell equipped with two face-to-face silicon detectors associated to one or two germanium detectors. Minimum Detectable activity Concentrations (MDCs) of environmental samples were calculated to be approximately 0.1 mBq/m(3) for the isotopes (131m)Xe, (133m)Xe, (133)Xe and 0.4 mBq/m(3) for (135)Xe (single germanium configuration). The detection system might be used to simultaneously measure particulate and noble gas samples from the CTBT International Monitoring System (IMS). That possibility could lead to new capacities for particulate measurements by allowing electron-photon coincidence detection of certain fission products.

On the use of (127)Xe standards for the quality control of CTBTO noble gas stations and support laboratories.

(127)Xe has a longer half-life than (131m)Xe, it can be easily purely produced and it is present in the environment at very low level. For these reasons, (127)Xe is supposed to be a convenient quality control radionuclide for remote noble gas stations of the International Monitoring System (IMS) network. As CEA/DAM has recently developed two new photon/electron setups for low-level detection of (131m)Xe, (133m)Xe, (133)Xe and (135)Xe, we took the opportunity to test these setups for the measurement of a (127)Xe standard. The results and a detailed description of these measurements are presented in this paper. They illustrate the complexity of (127)Xe decay, emitting simultaneously several γ, X-rays, conversion electrons and Auger electrons; this results in highly summated coincidence spectra. The measurements performed provide precise electron energy calibration of the setups. The count rate of electrons in coincidence with iodine Kα X-rays was found to be surprisingly low, leading to the study of electron-gated photon spectrum. Finally, a comparison of three photon/electron coincidence spectra obtained with three different setups is given. The use of (127)Xe as a standard for energy calibration of IMS noble gas station is possible, but it appears to be quite complicated for efficiency check of noble gas station equipped with ß/γ detectors.

Improvements of low-level radioxenon detection sensitivity by a state-of-the art coincidence setup.

The ability to quantify isotopic ratios of 135, 133 m, 133 and 131 m radioxenon is essential for the verification of the Comprehensive Nuclear-Test Ban Treaty (CTBT). In order to improve detection limits, CEA has developed a new on-site setup using photon/electron coincidence (Le Petit et al., 2013. J. Radioanal. Nucl. Chem., DOI : 10.1007/s 10697-013-2525-8.). Alternatively, the electron detection cell equipped with large silicon chips (PIPS) can be used with HPGe detector for laboratory analysis purpose. This setup allows the measurement of ß/γ coincidences for the detection of (133)Xe and (135)Xe; and K-shell Conversion Electrons (K-CE)/X-ray coincidences for the detection of (131m)Xe, (133m)Xe and (133)Xe as well. Good energy resolution of 11 keV at 130 keV and low energy threshold of 29 keV for the electron detection were obtained. This provides direct discrimination between K-CE from (133)Xe, (133m)Xe and (131m)Xe. Estimation of Minimum Detectable Activity (MDA) for (131m)Xe is in the order of 1mBq over a 4 day measurement. An analysis of an environmental radioxenon sample using this method is shown.

Innovative concept for a major breakthrough in atmospheric radioactive xenon detection for nuclear explosion monitoring.

The verification regime of the comprehensive test ban treaty (CTBT) is based on a network of three different waveform technologies together with global monitoring of aerosols and noble gas in order to detect, locate and identify a nuclear weapon explosion down to 1 kt TNT equivalent. In case of a low intensity underground or underwater nuclear explosion, it appears that only radioactive gases, especially the noble gas which are difficult to contain, will allow identification of weak yield nuclear tests. Four radioactive xenon isotopes, 131mXe, 133mXe, 133Xe and 135Xe, are sufficiently produced in fission reactions and exhibit suitable half-lives and radiation emissions to be detected in atmosphere at low level far away from the release site. Four different monitoring CTBT systems, ARIX, ARSA, SAUNA, and SPALAX™ have been developed in order to sample and to measure them with high sensitivity. The latest developed by the French Atomic Energy Commission (CEA) is likely to be drastically improved in detection sensitivity (especially for the metastable isotopes) through a higher sampling rate, when equipped with a new conversion electron (CE)/X-ray coincidence spectrometer. This new spectrometer is based on two combined detectors, both exhibiting very low radioactive background: a well-type NaI(Tl) detector for photon detection surrounding a gas cell equipped with two large passivated implanted planar silicon chips for electron detection. It is characterized by a low electron energy threshold and a much better energy resolution for the CE than those usually measured with the existing CTBT equipments. Furthermore, the compact geometry of the spectrometer provides high efficiency for X-ray and for CE associated to the decay modes of the four relevant radioxenons. The paper focus on the design of this new spectrometer and presents spectroscopic performances of a prototype based on recent results achieved from both radioactive xenon standards and air sample measurements. Major improvements in detection sensitivity have been reached and quantified, especially for metastable radioactive isotopes 131mXe and 133mXe with a gain in minimum detectable activity (about 2 × 10-3 Bq) relative to current CTBT SPALAX™ system (air sampling frequency normalized to 8 h) of about 70 and 30 respectively.

Low-level activity measurement of 131Xem, 133Xem, 135Xe and 133Xe in atmospheric air samples using high-resolution dual X-gamma spectrometry.

High-resolution dual X and gamma spectrometry has been optimized to improve the sensitivity in analyzing radioxenon from environmental samples, especially for the metastable isotopes (131Xem and 133Xem). The full-energy peak (FEP) efficiency curve in the 20-700 keV range has been established with a global uncertainty better than +/-3% using a Monte Carlo simulation. The minimum detectable activity concentrations (MDC) achievable at the laboratory for 131Xem, 133Xem, 133Xe and 135Xe are presented and the influence of 133Xe activity on the metastable radioxenon MDCs is evaluated.

Activity measurement of a 176Lu sample using coincidence peaks and Monte Carlo simulations.

We present the results of the activity measurement of a sample of the rare isotope 176Lu, obtained by gamma-ray spectrometry through the use of 22 peaks in an energy spectrum acquired with a 300 cc well-type HPGe detector located in the Modane underground facility below the French Alps. Of the above peaks, 17 are coincidence peaks between two or three gamma-rays or X-rays. True coincidence summing corrections were made using our Coincal code. Monte Carlo simulations were carried out for calibration purposes.

Certified reference material for radionuclides in fish flesh sample IAEA-414 (mixed fish from the Irish Sea and North Sea).

A certified reference material (CRM) for radionuclides in fish sample IAEA-414 (mixed fish from the Irish Sea and North Seas) is described and the results of the certification process are presented. Nine radionuclides (40K, 137Cs, 232Th, 234U, 235U, 238U, 238Pu, 239+240Pu and 241Am) were certified for this material. Information on massic activities with 95% confidence intervals is given for six other radionuclides (90Sr, 210Pb(210Po), 226Ra, 239Pu, 240Pu 241Pu). Less frequently reported radionuclides (99Tc, 129I, 228Th, 230Th and 237Np) and information on some activity and mass ratios are also included. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in fish sample, for the development and validation of analytical methods and for training purposes. The material is available from IAEA, Vienna, in 100 g units.

Monte Carlo calculation of the efficiency calibration curve and coincidence-summing corrections in low-level gamma-ray spectrometry using well-type HPGe detectors

Well-type high-purity germanium (HPGe) detectors are well suited to the analysis of small amounts of environmental samples, as they can combine both low background and high detection efficiency. A low-background well-type detector is installed in the Modane underground Laboratory. In the well geometry, coincidence-summing effects are high and make the construction of the full energy peak efficiency curve a difficult task with an usual calibration standard, especially in the high energy range. Using the GEANT code and taking into account a detailed description of the detector and the source, efficiency curves have been modelled for several filling heights of the vial. With a special routine taking into account the decay schemes of the radionuclides, corrections for coincidence-summing effects that occur when measuring samples containing 238U, 232Th or 134Cs have been computed. The results are found to be in good agreement with the experimental data. It is shown that triple coincidences effect on counting losses accounts for 7-15% of pair coincidences effect in the case of 604 and 796 keV lines of 134Cs.

The absolute and relative bioavailability of dipyridamole from different preparations and the in vitro-in vivo comparison.

The in vitro liberation and the bioavailability (BV) of dipyridamole (D) in three different brands (A, B, C) were determined in a three way cross-over study on 12 healthy subjects. Also, the pharmacokinetics of D given intravenously was investigated. The in vitro liberation of B is only to be achieved by repeated touching. The tmax for the preparations, expressed as mean +/- s mean amounts as follows: A: 0.8 +/- 0.06; B: 1.1 +/- 0.1; C: 0.8 +/- 0.09 hours and is in the case of B significantly different (p less than 0.05) from the others. The cmax values (A: 1.01 +/- 0.25; B: 1.16 +/- 0.15; C: 1.51 +/- 0.3 mumol X l-1) and the AUC values (A: 3.8 +/- 0.9; B: 3.1 +/- 0.5; C: 3.8 +/- 0.7 mumol X h X l-1) are not different. The absolute BV of D is 27 +/- 5.5% (range: 11-44%) independent of the used brand. In 4 subjects a second tmax at the 4th-6th hour is to be observed irrespective of the way of dosing. An enterohepatic circulation is assumed. It is concluded that the determination of the in vitro liberation is a necessary and useful parameter, but cannot be used alone for characterization of the BV in every case, as e.g., for problem drugs.

[In vitro and in vivo studies of diclofenac suppositories in humans]. / Zur Beziehung von in-vitro- und in-vivo-Untersuchungen beim Menschen am Beispiel von Diclofenac-Suppositorien.

Five different preparations of diclofenac-suppositories (A, B, C, D, E) are investigated for in vitro liberation (modified paddle method) and for in vivo bioavailability in man (8-12 subjects) in a crossover design. In vitro, the time at which 63.2% of the drug are liberated (tL) is 14, 20, 25, 14 and 3.5 min for the preparations A, B, C, D and E, respectively. The steady state concentrations from the preparations B and C are 51 and 11%, respectively, and lower than for the others. In vivo, the time of the concentration maximum (tmax) in min is (mean +/- S mean): A = 68 +/- 18, B = 72 +/- 9, C = 120 +/- 22, D = 42 +/- 3, E = 24 +/- 0.5. The concentration maximum (cmax) in mumol . l-1 at tmax is (mean +/- S mean): A = 5.9 +/- 0.8, B = 3.9 +/- 0.3, C = 3.1 +/- 0.4, D = 5.7 +/- 0.6, and E = 5.5 +/- 0.8. The area under the curve (AUC) for all the preparations has found to be between 8.7 and 10,6 mumol . h . l-1. There is a significant correlation between the in vitro parameter tL and the in vivo data of tmax and cmax, respectively. In consequence, the invasion behaviour in vivo can be derived from in vitro data for drugs with similar good physicochemical properties as diclofenac-Na.

The in vitro liberation and the bioavailability of different brands of griseofulvin in plasma and urine in man.

The bioavailability of griseofulvin in three different brands, two microfine forms (Gricin = G, Likuden = L), and one ultramicrofine form (Gris-PEG = GP), was determined in plasma and urine in six healthy volunteers in a crossover study and compared with in vitro liberation data. GP shows a higher AUCo infinity (140 +/- 24 mumol . h . l-1) and Cmax (4.5 +/- 0.1 mumol . h-1) than the microsize brands of griseofulvin (AUCo infinity:58 +/- 7, and 45 +/- 6 mumol . h . l-1; Cmax:1.7 +/- 0.2, and 1.5 +/- 0.2 mumol . l-1; G and L, resp.), but the same tmax at the third hour. There results correspond with the in vitro liberation data. Contradictory results of the bioavailability are found by determining the amount of 6-Demethylgriseofulvin eliminated in urine. The elimination of this main metabolite after dosing with L is lower (0.18 +/- 0.02 mmol) than those of the other two brands, which do not differ (0.31 +/- 0.04; 0.32 +/- 0.02 mmol, G and GP, resp.). It is concluded that the determination of bioavailability only by means of the eliminated amount of a metabolite in urine may produce false results.

On the distribution of drugs in saliva and blood plasma.

The equilibration of drug concentrations between blood plasma (unbound part) and saliva was studied for selected drugs with different physicochemical properties: Quinidine, sulfamerazine, paracetamol, diazepam and ethanol. From these and other experimental results it is suggested: 1. The concentration ratio between saliva and blood plasma (unbound) can only equal one for basic drugs with a pK a lower than 5.5 and acid drugs with a pK a higher than 8.5 and for pH indifferent drugs. 2. The drug must have a sufficient permeation ability through lipid membranes, valuable by the lipid water partition coefficient.