Search

The KArlsruhe TRItium Neutrino (KATRIN) experiment aims to search for the effective electron antineutrino mass with a sensitivity of 0.2 eV (90 % C.L.). In order to achieve this goal, KATRIN measurement phases focusing on the neutrino mass search are alternated with phases of investigations of systematic effects. During these phases, metastable $^{83\mathrm{m}}$Kr is used as a calibration source. The monoenergetic conversion electrons emitted accompanying the decay of $^{83\mathrm{m}}$Kr allow a direct access to the starting conditions of $\beta$-electrons produced inside the windowless gaseous tritium source (WGTS) of KATRIN. To make use of $^{83\mathrm{m}}$Kr in the WGTS, the Tritium Loop System, which provides a stable flow of tritium to the WGTS, needs to be operated in special modes. This paper focuses on the technical implementation of these modes and their performance with regard to the achievable $^{83\mathrm{m}}$Kr-rates, gas densities, and gas compositions inside the WGTS., Comment: 24 pages, 13 figures

We show the synthesis of an in vivo stable mercury compound with functionality suitable for radiopharmaceuticals. The designed cyclic bisarylmercury was based on the water tolerance of organomercurials, higher bond dissociation energy of Hg−Ph to Hg−S, and the experimental evidence that acyclic structures suffer significant cleavage of one of the Hg−R bonds. The bispidine motif was chosen for its in vivo stability, chemical accessibility, and functionalization properties. Radionuclide production results in 197(m)HgCl2(aq), so the desired mercury compound was formed via a water‐tolerant organotin transmetallation. The Hg‐bispidine compound showed high chemical stability in tests with an excess of sulfur‐containing competitors and high in vivo stability, without any observable protein interaction by human serum assay, and good organ clearance demonstrated by biodistribution and SPECT studies in rats. In particular, no retention in the kidneys was observed, typical of unstable mercury compounds. The natHg analogue allowed full characterization by NMR and HRMS., Stable and versatile: The cyclic bisarylmercury bispidine structure shows exceptional stability against sulfur compounds known to usually react very easily with mercury. Aside from its novelty in mercury chemistry, the in vivo stability paired with the functionalizability of this motif is an important step forward in the development of useful radiomercury pharmaceuticals.

Excitation functions of the reactions natTi(p,x)48V, 43Sc, 44gSc, 44mSc, 46m+gSc, 47Sc, 48Sc and natCu(p,x)62Zn, 63Zn, 65Zn, 61Cu, 58m+gCo were measured in the energy interval of 6.4–36.0 MeV (titanium) and 7.3–35.9 MeV (copper) with use of stacked-foil technique and off-line γ-ray spectrometry. The results were compared with previously published experimental data and with prediction of the nuclear reaction model code TALYS adopted from the TENDL-2019 online library. Thick target yields were calculated from the obtained cross-sections. Finally, we fit the selected experimental data sets for the natTi(p,x)48V and natCu(p,x)62,63,65Zn reactions and compare the results with the IAEA recommended cross-sections.

We have recently re-measured excitation functions of proton- and deuteron-induced nuclear reactions on 197Au focused particularly on theranostic 197m,gHg. The γ-ray spectra evaluation revealed inconsistency in the γ-line emission probabilities of 197mHg. Detailed measurements of the separated 197m,gHg samples resulted in a thorough revision of the 197mHg decay scheme. In this short summary, we provide cross-sections, isomeric ratios and the yields of 197mHg and 197gHg corrected for the new decay data.

Cyclotrons used to produce medical isotopes are relatively widespread. Nowadays, it is popular to place small and compact accelerators directly in hospitals. This approach simplifies handling of the produced radiopharmaceuticals, but it imposes strict radiation safety measures during production. For optimal utilization of isotope production cyclotrons, the exact knowledge of leakage neutron field is essential due to the deep penetration ability of the high energy neutrons and the accompanied secondary radiation production. Our paper presents measurement of the neutron leakage spectra for various angles from an open target assembly at the cyclotron U-120M at NPI of CAS. These spectra are compared with data obtained from a compact medical cyclotron IBA Cyclone 18/9 in UJV Rez and also with activation measurements of reactions with different threshold energies. All data were also compared with calculations made with different Monte Carlo codes using both models and data libraries. The preliminary results show significant disagreement between experiments and theoretical predictions. These findings could have implications not only to the nuclear data community but also to the production accelerators operators at the licensing stage.

Theranostic 197m,gHg of high specific activity may be produced by proton or deuteron activation of gold. The particle choice affects the isomeric ratio. In order to compare both projectiles, we re-measured cross-sections of the nuclear reactions 197Au(d,x)197mHg, 197gHg, 198mAu, 198gAu, 196m2Au, 196m1+gAu in the energy range of 8.3–19.7 MeV having employed usual stacked-foil method. The obtained values were compared with previously measured data and with prediction of the TALYS nuclear reaction model code adopted from the TENDL-2017 library. Experimental data were used for calculation of the thick target yields. The yields for the isomeric pair 197m,gHg were confronted with those for recently re-measured proton-induced reactions. We also provide a new data set for the reaction natCu(d,x)63Zn.

We measured cross-sections of the nuclear reactions 197Au(p,x)197mHg, 197gHg, 195mHg, 195gHg, 196m2Au, 196m1+gAu, 194m+gAu in the energy range of 6.4–35.3 MeV having used stacked-foil technique with high purity gold foils. The results were compared with previously published data and with prediction of the TALYS nuclear reaction model code adopted from the TENDL-2017 library. Thick target yields were deduced from the measured data. Production of the theranostic isomeric pair 197m,gHg is thoroughly discussed.

The KArlsruhe TRItium Neutrino (KATRIN) experiment, which aims to make a direct and model-independent determination of the absolute neutrino mass scale, is a complex experiment with many components. More than 15 years ago, we published a technical design report (TDR) [https://publikationen.bibliothek.kit.edu/270060419] to describe the hardware design and requirements to achieve our sensitivity goal of 0.2 eV at 90% C.L. on the neutrino mass. Since then there has been considerable progress, culminating in the publication of first neutrino mass results with the entire beamline operating [arXiv:1909.06048]. In this paper, we document the current state of all completed beamline components (as of the first neutrino mass measurement campaign), demonstrate our ability to reliably and stably control them over long times, and present details on their respective commissioning campaigns., Comment: Added missing acknowledgement, corrected performance statement in chapter 4.2.5, updated author list and references

We report on the light sterile neutrino search from the first four-week science run of the KATRIN experiment in~2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are analyzed by a high-resolution MAC-E filter down to 40 eV below the endpoint at 18.57 keV. We consider the framework with three active neutrinos and one sterile neutrino of mass $m_{4}$. The analysis is sensitive to a fourth mass state $m^2_{4} \lesssim$ 1000 eV$^2$ and to active-to-sterile neutrino mixing down to $|U_{e4}|^2 \gtrsim 2\cdot10^{-2}$. No significant spectral distortion is observed and exclusion bounds on the sterile mass and mixing are reported. These new limits supersede the Mainz results and improve the Troitsk bound for $m^2_{4}, Comment: 8 pages, 4 figures

Prostate specific membrane antigen (PSMA) is a type II membrane protein widely expressed on the surface of prostate cancer cells. One of its functions is to act as a receptor mediating the ligand internalization. This PSMA property is employed in the diagnostics and therapy of prostate cancer. Over the years, small molecules with high affinity for PSMA have been developed and labelled with positron emitters (e.g.ARecovery ofA new method of labelling PSMA-11 ligand with

The KArlsruhe TRItium Neutrino experiment (KATRIN) aims to determine the effective electron (anti)neutrino mass with a sensitivity of $0.2\textrm{ eV/c}^2$ (90$\%$ C.L.) by precisely measuring the endpoint region of the tritium $\beta$-decay spectrum. It uses a tandem of electrostatic spectrometers working as MAC-E (magnetic adiabatic collimation combined with an electrostatic) filters. In the space between the pre-spectrometer and the main spectrometer, an unavoidable Penning trap is created when the superconducting magnet between the two spectrometers, biased at their respective nominal potentials, is energized. The electrons accumulated in this trap can lead to discharges, which create additional background electrons and endanger the spectrometer and detector section downstream. To counteract this problem, "electron catchers" were installed in the beamline inside the magnet bore between the two spectrometers. These catchers can be moved across the magnetic-flux tube and intercept on a sub-ms time scale the stored electrons along their magnetron motion paths. In this paper, we report on the design and the successful commissioning of the electron catchers and present results on their efficiency in reducing the experimental background., Comment: - 12 pages, 14 figures, LaTeX; typos corrected, references added; precised a few arguments, added additional discussions, results unchanged

Purpose The purpose of this study was to evaluate a set of widely used nuclear medicine imaging agents as possible methods to study the early effects of systemic inflammation on the living brain in a mouse model of sepsis-associated encephalopathy (SAE). The lipopolysaccharide (LPS)-induced murine systemic inflammation model was selected as a model of SAE. Procedures C57BL/6 mice were used. A multimodal imaging protocol was carried out on each animal 4 h following the intravenous administration of LPS using the following tracers: [99mTc][2,2-dimethyl-3-[(3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(3E)-3-hydroxyiminobutan-2-yl]azanide ([99mTc]HMPAO) and ethyl-7-[125I]iodo-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate ([125I]iomazenil) to measure brain perfusion and neuronal damage, respectively; 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) to measure cerebral glucose uptake. We assessed microglia activity on another group of mice using 2-[6-chloro-2-(4-[125I]iodophenyl)-imidazo[1,2-a]pyridin-3-yl]-N-ethyl-N-methyl-acetamide ([125I]CLINME). Radiotracer uptakes were measured in different brain regions and correlated. Microglia activity was also assessed using immunohistochemistry. Brain glutathione levels were measured to investigate oxidative stress. Results Significantly reduced perfusion values and significantly enhanced [18F]FDG and [125I]CLINME uptake was measured in the LPS-treated group. Following perfusion compensation, enhanced [125I]iomazenil uptake was measured in the LPS-treated group’s hippocampus and cerebellum. In this group, both [18F]FDG and [125I]iomazenil uptake showed highly negative correlation to perfusion measured with ([99mTc]HMPAO uptake in all brain regions. No significant differences were detected in brain glutathione levels between the groups. The CD45 and P2Y12 double-labeling immunohistochemistry showed widespread microglia activation in the LPS-treated group. Conclusions Our results suggest that [125I]CLINME and [99mTc]HMPAO SPECT can be used to detect microglia activation and brain hypoperfusion, respectively, in the early phase (4 h post injection) of systemic inflammation. We suspect that the enhancement of [18F]FDG and [125I]iomazenil uptake in the LPS-treated group does not necessarily reflect neural hypermetabolism and the lack of neuronal damage. They are most likely caused by processes emerging during neuroinflammation, e.g., microglia activation and/or immune cell infiltration. Electronic supplementary material The online version of this article (10.1007/s11307-018-1201-3) contains supplementary material, which is available to authorized users.

Specific oncology diagnostics requires new types of the selective radiopharmaceuticals, particularly those suitable for the molecular PET imaging. The aim of this work is to present a new, specific PET-immunodiagnostic radiopharmaceutical based on the monoclonal antibody IgG M75 targeting human carbonic anhydrase IX labelled with 64Cu (T½ = 12.70h) and its in vitro and in vivo evaluation. The antibody IgG M75 was conjugated with a non-commercial copper-specific chelator "phosphinate" and then labelled with the positron emitter 64Cu. Stability of the labelled conjugated was tested in human serum. The immunoreactivity of the labelled conjugate was evaluated in vitro on a suitable cell cultures of the colorectal carcinoma (HT-29) and its imaging properties were estimated in vivo on a mouse model with inoculated colorectal carcinoma HT-29 imaged on a µPET/CT. The tested radioimmunoconjugate was obtained in a specific activity of 0.25-0.5 MBq/µg. In vitro uptake experiments revealed specific binding to the HT-29 cells (45 ± 2.8% of the total added activity) and the measured KD value was found to be 9.2nM. Imaging clearly demonstrated significant uptake of the labelled monoclonal antibody in the tumour at 18h post administration. The radioimmunoconjugate 64Cu-PS-IgG M75 seems to be a suitable candidate for PET diagnostics of hypoxic tumours expressing human carbonic anhydrase IX.

We show that use of the radionuclide 56Co for calibration of the full energy peak efficiency, e, of a coaxial HPGe detector, in addition to the commonly employed set of activity standards (133Ba, 241Am, 152Eu, 57Co, 137Cs, 88Y, 65Zn), affects significantly the e values in the high energy region. This change resulted in substantial improvement of the accuracy of Ca determination by k 0-INAA via the 49Ca radionuclide, which emits predominantly the 3084 keV photons, as demonstrated by Ca results in NIST SRMs 1547 Peach Leaves, 1633b constituent elements in coal fly ash, and 2711 Montana II Soil.

The determination of the neutrino mass is one of the major challenges in astroparticle physics today. Direct neutrino mass experiments, based solely on the kinematics of $$\upbeta $$β-decay, provide a largely model-independent probe to the neutrino mass scale. The Karlsruhe Tritium Neutrino (KATRIN) experiment is designed to directly measure the effective electron antineutrino mass with a sensitivity of $$0.2\hbox { eV}$$0.2eV ($$90\%$$90% CL). In this work we report on the first operation of KATRIN with tritium which took place in 2018. During this commissioning phase of the tritium circulation system, excellent agreement of the theoretical prediction with the recorded spectra was found and stable conditions over a time period of 13 days could be established. These results are an essential prerequisite for the subsequent neutrino mass measurements with KATRIN in 2019.

The cross-sections of the

In this work, we present the first spectroscopic measurements of conversion electrons originating from the decay of metastable gaseous $^\mathrm{83m}$Kr with the Karlsruhe Tritium Neutrino (KATRIN) experiment. The results obtained in this calibration measurement represent a major commissioning milestone for the upcoming direct neutrino mass measurement with KATRIN. The successful campaign demonstrates the functionalities of the full KATRIN beamline. The KATRIN main spectrometer's excellent energy resolution of ~ 1 eV made it possible to determine the narrow K-32 and L$_3$-32 conversion electron line widths with an unprecedented precision of ~ 1 %., Fixed affiliation of the corresponding author

An IAEA coordinated research project that began in 2012 and ended in 2016 was primarily dedicated to the compilation, evaluation and recommendation of cross-section data for the production of medical radionuclides. One significant part of this work focused on diagnostic positron emitters. These particular studies consist of 69 reactions for direct and indirect or generator production of 44Sc(44Ti), 52mMn(52Fe), 52gMn, 55Co, 61Cu, 62Cu(62Zn), 66Ga, 68Ga(68Ge), 72As(72Se), 73Se, 76Br, 82Rb(82Sr), 82mRb, 86Y, 89Zr, 90Nb, 94mTc, 110mIn(110Sn), 118Sb(118Te), 120I, 122I(122Xe), 128Cs(128Ba), and 140Pr(140Nd) medical radionuclides. The resulting reference cross-section data were obtained from Pade fits to selected and corrected experimental data, and integral thick target yields were subsequently deduced. Uncertainties in the fitted results were estimated via a Pade least-squares method with the addition of a 4% assessed systematic uncertainty. Experimental data were also compared with theoretical predictions available from the TENDL-2015 and TENDL-2017 libraries. All of the numerical reference cross-section data with their corresponding uncertainties and deduced integral thick target yields are available on-line at the IAEA-NDS medical portal www-nds.iaea.org/medicalportal and also at the IAEA-NDS web page www-nds.iaea.org/medical/positron_emitters.html .

International audience; Increasing interest in the treatment of human disease by means of targeted radionuclide-based therapies requires an accurate understanding of achievable yields and quantification of realisable degrees of purity. Important studies within a more extensive Coordinated Research Project of the International Atomic Energy Agency (IAEA CRP) have included in-depth assessments and evaluations of all available measured cross-section data for ten nuclear reactions leading to the formation of $^{131}$Cs, $^{131}$Ba, $^{225}$Ac, $^{225}$Ra, $^{227}$Th, $^{227}$Ac, $^{230}$U and $^{230}$Pa for various on-going and proposed therapeutic applications in nuclear medicine. Equivalent studies were also undertaken of possible reactions to produce the $^{178}$W/low-spin $^{178m}$Ta generator system that has been clinically applied in diagnosis by means of SPECT - these particular cross-section studies and recommendations are included in this paper for completeness. All available measured data have been critically reviewed and assessed to produce statistically consistent datasets. Selected datasets have been fitted by a least-squares method with Padé approximations of variable order to evaluate the production cross sections and corresponding uncertainties. New measurements have been made in some instances, and reported data have been adjusted to accommodate new nuclear decay or monitor reaction data which altered the original reported quantities adversely. Insufficient measured data are available in many cases to permit a reliable evaluation of cross sections, and these instances are discussed. Recommended therapeutic radionuclide production reaction data and their uncertainties are available on the Web page of the IAEA Nuclear Data Section at www-nds.iaea.org/radionuclides/ and also at the IAEA medical portal www-ds.iaea.org/medportal/

Background Prostate specific membrane antigen (PSMA) is a type II membrane protein widely expressed on the surface of prostate cancer cells. One of its functions is to act as a receptor mediating the ligand internalization. This PSMA property is employed in the diagnostics and therapy of prostate cancer. Over the years, small molecules with high affinity for PSMA have been developed and labelled with positron emitters (e.g. 68Ga, 18F, 11C, 64Cu, or 86Y). One of these radiolabelled ligands, [68Ga] PSMA-11, is one of the most widespread tracers for PET imaging of the prostate cancer. Many techniques have been proposed and tested for the 68Ga labelling of PSMA-11. The aim of our work was to design a labelling method of PSMA-11 that minimizes number of the used chemicals and steps, providing quantitative labelling yield at laboratory temperature and may be easily automated. Methodology A68Ge/68Ga generator eluate in 0.1 M HCl was loaded on an activated Oasis MCX cartridge, and the cartridge was then thoroughly washed with water. The radionuclide 68Ga was eluted from the cartridge with 0.1 M NaHCO3 (pH = 8.5, n = 36) or with the same solution with pH adjusted to 7.2–9.0 (n = 38). Precursor PSMA-11 was mixed directly with the cartridge eluate of 68Ga in 0.1 M NaHCO3 of given pH. For the stability test, samples of 68GaPSMA-11 in 0.1 M NaHCO3 (pH 8.5) were mixed in ratio 1 : 1 with the following solutions: 0.1 M NaHCO3 (pH 8.5), human serum, PBS and 0.9% NaCl. In order to estimate an effect of the time elapsed between 68Ga elution from the cartridge in 0.1 M NaHCO3 (pH 8.5) and the labelling onset of PSMA-11, the latter was initiated 0, 5, 10 and 20 min post elution and radiochemical yield was monitored. All the PSMA-11 labelled samples were subjected to radiochemical purity test using HPLC. The whole process starting from generator elution up to HPLC analysis commencement took 10–15 min. Results Recovery of 68Ga from cartridge Oasis MCX using 0.1 M NaHCO3 at pH 8.5 was 71.5 ± 1.4%. Thirty six PSMA-11 samples (10 μg in reaction mixture) were labelled at pH 8.5 with total average radiochemical yield of 98 ± 2%. Recovery of 68Ga from cartridge Oasis MCX using 0.1 M NaHCO3 at variable pH of 7.2–9.0 was 62.5 ± 1.8% showing certain decrease with decreasing pH. A total of 138 samples of PSMA-11 were labelled with 68 Ga at variable pH (7.2–9.0) and four different amounts of PSMA-11 (1, 2.5, 5 and 10 μg) resulting in the labelling yields of 54.0 ± 5.3%, 88.2 ± 3.2%, 99.4 ± 0.3% and 99.9 ± 0.1%, respectively. Irrespective of the pH, the radiolabelling yield was quantitative for the molar ratio PSMA-11: 68Ga > 5000 : 1 in the reaction mixture. Stability tests in 0.1 M NaHCO3 (pH 8.5), human serum, PBS and 0.9% NaCl revealed no observable release of 68Ga from the 68Ga-PSMA-11 complex within 3 h. Similarly, the delay between the 68Ga elution from the Oasis MCX cartridge in 0.1 M NaHCO3 (pH 8.5) and start of the labelling of PSMA-11 labelling has no effect on the radiochemical yield. Conclusion A new method of labelling PSMA-11 ligand with 68Ga in 0.1 M NaHCO3 using Oasis MCX cartridges was proposed, developed and tested. The results demonstrated that it is rapid, simple, reproducible and easy to automate.

In the framework of the Co-ordinated Research Project of the IAEA, we measured in detail cross-sections of the nuclear reactions natMo(p,x)93gTc, 93mTc, 93m+gTc, 94gTc, 94mTc, 95gTc, 95mTc, 96m+gTc, 97mTc, 99mTc, 90Mo, 93mMo, 99Mo, 88gNb, 88mNb, 89gNb, 89mNb, 90m+gNb, 90m+gNbcum, 91mNb, 92mNb, 95gNb, 95mNb, 95m+gNb, 96Nb, 97m+gNb, 88m+gZrcum and 89m+gZrcum in the energy range of 6.9–35.8 MeV. The data for formation of 97mTc, 88gNb, 88mNb and 89mNb are reported for the first time. The obtained results were compared to the prediction of the nuclear reaction model code TALYS adopted from the TENDL-2015 library and to the previously published cross-sections. The thick target yields for all the radionuclides were calculated from the measured data. We suggest recommended cross-sections and thick target yields for the 100Mo(p,2n)99mTc, 100Mo(p,x)99Mo and natMo(p,x)96m+gTc nuclear reactions deduced from the selected experimental data.

Gamma rays following the decay of the 197 g Hg and 197 m Hg radionuclides were measured using chemically-purified sources and a planar HPGe detector. In the case of 197 m Hg, precise values of 94.68 (9)% and 5.32 (9)% were determined for the IT and EC branches, respectively, the latter found to differ significantly from previously published data. The half-lives of 197 g Hg and 197 m Hg were also measured as 64.81 (24) h and 23.82 (4) h.

The cross-sections of the natTi(3He,x)48V,48Cr and the 165Ho(3He,xn)166,165,163Tm reactions were measured from the threshold to 47 MeV using well-established method of stacked-foil activation and off-line γ-ray spectrometry. The 3He-ion induced nuclear reaction cross-sections on 165Ho were measured for the first time. Their comparison with the prediction adopted from the TENDL-2017 library revealed significant difference. Thick target yields deduced from the experimental data are provided.

Human carbonic anhydrase IX is a membrane enzyme that is significantly expressed in some types of cancer cells, while copper radioisotopes offer wide range of diagnostic, therapeutic and theranostic properties. The work was focused on a new approach to the labelling of antibody IgG M75 for epitope human carbonic anhydrase IX with copper radioisotopes

The Karlsruhe Tritium Neutrino (KATRIN) experiment is a large-scale effort to probe the absolute neutrino mass scale with a sensitivity of 0.2 eV (90% confidence level), via a precise measurement of the endpoint spectrum of tritium β-decay. This work documents several KATRIN commissioning milestones: the complete assembly of the experimental beamline, the successful transmission of electrons from three sources through the beamline to the primary detector, and tests of ion transport and retention. In the First Light commissioning campaign of autumn 2016, photoelectrons were generated at the rear wall and ions were created by a dedicated ion source attached to the rear section; in July 2017, gaseous83mKr was injected into the KATRIN source section, and a condensed83mKr source was deployed in the transport section. In this paper we describe the technical details of the apparatus and the configuration for each measurement, and give first results on source and system performance. We have successfully achieved transmission from all four sources, established system stability, and characterized many aspects of the apparatus., United States. Department of Energy (Grant DEFG02-97ER41020), United States. Department of Energy (Grant DE-FG02-94ER40818), United States. Department of Energy (Grant DE-SC0004036), United States. Department of Energy (Grant DE-FG02-97ER41033), United States. Department of Energy (Grant DE-FG02- 97ER41041), United States. Department of Energy (Grant DE-AC02-05CH11231), United States. Department of Energy (Grant DE-SC0011091)

Arenz, M., et al. “Reduction of Stored-Particle Background by a Magnetic Pulse Method at the KATRIN Experiment.” The European Physical Journal C, vol. 78, no. 9, Sept. 2018. © 2018 The Authors, United States. Department of Energy (DE-FG02-97ER41020), United States. Department of Energy (DE-FG02-94ER40818), United States. Department of Energy (DE-SC0004036), United States. Department of Energy (DE-FG02-97ER41033), United States. Department of Energy (DE-FG02-97ER41041), United States. Department of Energy (DEAC02-05CH11231), United States. Department of Energy (DE-SC0011091)

International audience; Evaluated cross sections of beam-monitor reactions are expected to become the de-facto standard for cross-section measurements that are performed over a very broad energy range in accelerators in order to produce particular radionuclides for industrial and medical applications. The requirements for such data need to be addressed in a timely manner, and therefore an IAEA coordinated research project was launched in December 2012 to establish or improve the nuclear data required to characterise charged-particle monitor reactions. An international team was assembled to recommend more accurate cross-section data over a wide range of targets and projectiles, undertaken in conjunction with a limited number of measurements and more extensive evaluations of the decay data of specific radionuclides. Least-square evaluations of monitor-reaction cross sections including uncertainty quantification have been undertaken for charged-particle beams of protons, deuterons, 3 He- and 4 He-particles. Recommended beam monitor reaction data with their uncertainties are available at the IAEA-NDS medical portal www-nds.iaea.org/medical/monitor_reactions.html .

The neutrino mass experiment KATRIN requires a stability of 3 ppm for the retarding potential at − 18.6 kV of the main spectrometer. To monitor the stability, two custom-made ultra-precise high-voltage dividers were developed and built in cooperation with the German national metrology institute Physikalisch-Technische Bundesanstalt (PTB). Until now, regular absolute calibration of the voltage dividers required bringing the equipment to the specialised metrology laboratory. Here we present a new method based on measuring the energy difference of two [superscript 83m]Kr conversion electron lines with the KATRIN setup, which was demonstrated during KATRIN’s commissioning measurements in July 2017. The measured scale factor M = 1972.449(10) of the high-voltage divider K35 is in agreement with the last PTB calibration 4 years ago. This result demonstrates the utility of the calibration method, as well as the long-term stability of the voltage divider., United States. Department of Energy (Grant DEFG02- 97ER41020), United States. Department of Energy (Grant DE-FG02-94ER40818), United States. Department of Energy (Grant DE-SC0004036), United States. Department of Energy (Grant DEFG02-97ER 41033), United States. Department of Energy (Grant DE-FG02-97ER41041), United States. Department of Energy (Grant DE-AC02-05CH11231), United States. Department of Energy (Grant DE-SC00 11091)

We measured cross-sections of the deuteron-induced reactions on 89 Y in the energy range of 3.9–19.5 MeV. Excitation functions for formation of 88 Zr, 89m Zr, 89 Zr, 88 Y, 90m Y and 87m Sr were determined and compared with previously published data and prediction of the TALYS code. Thick target yields for production of 88 Zr, 89 Zr cum , 88 Y, 90m Y and 87m Sr were calculated from the measured cross-sections. Achievable activity versus radionuclidic purity of medically relevant 89 Zr is discussed and compared with the production via the 89 Y(p,n) reaction. Parallel use of titanium and aluminium beam monitors revealed systematic difference between the recommended cross-sections of both monitoring reactions and provided new cross-section data for formation of 24 Na, 27 Mg, 43 Sc, 44m Sc, 44 Sc, 46 Sc, 47 Sc and 48 Sc. The cross-sections for the nat Ti(d,x) 46 Sc reactions agree very well with recently proposed recommended values.

The production and separation of no-carrier-added 197(m)Hg for imaging and therapy research based on the 197Au(p,n)197(m)Hg reaction was recently reported. However, large-scale production requires the development of a rapid, reliable method for Hg/Au separation. Ideally, a solid phase sorbent is used to bind at least one of the two metal ions reversibly, allowing for the product elution into a small volume. Di(2-ethylhexyl)orthophosphoric acid (HDEHP) im-pregnated onto an inert support as the so called LN resin (LaNthanides) was examined for this application.

The KATRIN experiment will probe the neutrino mass by measuring the β-electron energy spectrum near the endpoint of tritium β-decay. An integral energy analysis will be performed by an electro-static spectrometer (``Main Spectrometer''), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240 m[superscript 3], and a complex inner electrode system with about 120 000 individual parts. The strong magnetic field that guides the β-electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300 °C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10[superscript −11] mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016., United States. Department of Energy (DE-FG02-97ER41020), United States. Department of Energy (DE-FG02-94ER40818), United States. Department of Energy (DE-SC0004036), United States. Department of Energy (DE-FG02-97ER41041), United States. Department of Energy (DE-FG02-97ER41033)

Drug delivery systems based on thermoresponsive polymers might serve as suitable carriers for local radiotherapy. We have, therefore, designed and synthesized a radioiodine-labellable thermoresponsive polymer. The polymer was synthesized by copolymerization of N -isopropylacrylamide with N -methacryloyl tyrosinamide in tetrahydrofuran, and then labelled by 131 I. The solution of this labelled polymer in dimethylsulfoxide (4.4 MBq/ml; 1.8 wt% polymer) was applied to femoral muscle of male Balb/C mice (50 μl per animal). The biodistribution and excretion of radioactivity was followed in 2 h and 1, 7, 14, 28 and 42 d post injection ( n =6 per time point). As expected, the labelled polymer was left on the application site (ca 90% 2 h post injection), decreasing slowly to ca 80% within 14 d. At 28 d post injection, ca 70% of the injected activity was still found on the application site, decreasing to ca 60% at 42 d. No organ-specific accumulation of the radioactivity released from the application site, including thyroid, was observed. Majority of the released radioactivity was excreted via urine and faeces. This preliminary study suggests that thermoresponsive polymers could be used as an effective delivery system for localized radiotherapy.

I. E. Marko [Universite catholique de Louvain, Belgium]—Novel Orthoesters in Organic Synthesis. S. J. Harwood [GlaxoSmithKline, UK]—The Synthesis of Stable Labelled Ketamine. Th. Moenius, R. Salter, B. Wietfeld, P. Burtscher, C. Zueger [Novartis, Switzerland]—C-13, C-14, N-15 Labelling of the 4-Cyanobenzyl bromide – A Versatile Labelling Building Block. J. Clayden [University of Manchester, UK]—Synthesis and Stereocontrol with Lithiated Amides. R. Salter, K. Bordeaux, P. Burtscher, Y. Metz, Th. Moenius, I. Rodriguez, R. Ruetsch, R. Voges, C. Zueger [Novartis, Switzerland]—Isotopic Labelling of STI571 and its Metabolites in the Development of Gleevec®. J. M. Gardiner, W. Stimpson, N. Panchal [University of Manchester, UK], J. Herbert, G. J. Ellames [Sanofi-Aventis, UK]—Synthesis of Labelled Carbohydrates. M. Beller [Rostock University, Germany]—Homogeneous Catalysis – A Powerful Tool for the Synthesis of Pharmaceuticals. J. Kozempel, J. Kadeřavek, L. Lesetický, O. Lebeda [University of Prague, Czech]—Preparation of Ortho-radiohalogenated Phenylazides and Triazenes, Versatile Building Blocks for Indirect Labelling. K. Wahala, P. Kiuru, E. Leppala, M. Pohjoispaa, K. Parikka, B. Raffaelli [University of Helsinki, Finland]—Controlled Polydeuteration of Estrogenic Compounds. J. M. Herbert [Sanofi-Aventis, UK]—Catalyst Stability in Iridium-mediated Isotope Exchange. C. G. M. Janssen, W.L.M. Verluyten, M. Vliegen [Johnson & Johnson Pharmaceutical, Belgium]—Pd/C Catalysed Hydrogenolytic H/T Exchange in Solvents, Effects on Solvents and Product in a Bromine-tritium Exchange Reaction. P. Mading, F. Fuchtner, R. Bergmann, J. Pietzsch, C. Hultsch, F. Wust [Forschungszentrum Rossendorf, Germany]—A New Module-Assisted Synthesis of the Versatile, Bifunctional Labelling Agent [18F]SFB: From Radiochemistry to Applications. M. Scheunemann, J. Vercouillie, St. Fischer, J. Steinbach [Institut fur Interdisziplinare Isotopenforschung Leipzig, Germany], D. Sorger, U. Grosmann, O. Sabri, R. Schliebs [University Leipzig, Germany]—Syntheses and First Biological Evaluation of 18F Labelled Bicyclic Analogues of Vesamicol as Potential VAChT Imaging Agents.

The mono-energetic conversion electrons from the decay of 83 m Kr represent a unique tool for energy calibration and systematic studies of the tritium beta spectrum measured in neutrino mass determination experiments. For this reason, the corresponding parent isotope was produced in reactions nat Kr(p,xn) 83 Rb. The behaviour of 83 Rb ( T 1 / 2 = 86.2 d ) and its daughter product 83 m Kr ( T 1 / 2 = 1.83 h ) was examined, when the 83 Rb was trapped in a cation-exchanger chromatographic paper or in zeolite. Using gamma spectroscopy measurements, recommendations for the production of a 83 Rb/ 83 m Kr radionuclide generator based on these cation-exchangers and suitable for the neutrino mass determination experiment KATRIN were deduced.

The alpha emitter (211)At is a radionuclide with good potential for use in the therapy of smaller tumours and metastases. However, limited availability of this radionuclide hinders development of this application and the research of astatine chemistry in general. In this general context we have designed and tested a new internal target system. A thin bismuth layer (3-5 microm) was evaporated onto a light target backing (7.5 g) and irradiated at 0.5-1.5 degrees angles with 29.5 MeV alpha particles beam of intensity up to 30 microA. The backing was then released from the target holder and used directly for astatine separation via dry distillation. Astatine condensed on the Teflon capillary walls was then eluted into 150-250 microl of methanol. The saturation yield was found to be ca. 400 MBq/microA, and the radionuclidic purity of (211)At acceptable for medical applications (activity ratio (210)At/(211)At

This paper deals with some technical aspects of the development and production of cyclotronmade radiopharmaceuticals (excluding PET). In this field, nuclear chemistry and pharmacy are in a close contact; therefore, requirements of the both should be taken into account. The principles of cyclotron targetry, separation/recovery of materials and synthesis of active substances are given, as well as issues connected with formulation of pharmaceutical forms. As the radiopharmaceuticals should fulfil the requirements on in vivo preparations, there exist a variety of demands pertaining to Good Manufacturing Practice (GMP) concept, which is also briefly discussed. A typical production chain is presented and practical examples of real technologies based on cyclotron-made radionuclides are given as they have been used in Nuclear Physics Institute of CAS (NPI). Special attention is devoted to the technology of enriched cyclotron targets. Frequently used medicinal products employing cyclotron-produced active substances are characterised (Rb/Kr generators, 123I-labelled MIBG, OIH and MAB's). The cyclotron produced radioactive implants for transluminal coronary angioplasty (radioactive stents) are introduced as an example of a medical device developed for therapeutic application.

Some of the cyclotron-produced radionuclides may serve as important materials for the production of radiopharmaceuticals. This lecture deals with basic information relating to various aspects of these compounds. In comparison with radionuclides/compounds used for non-medical purposes, radiopharmaceuticals are subject to a broader scale of regulations, both from the safety and efficacy point of view; besides that, there are both radioactive and medical aspects that must be taken into account for any radiopharmaceutical. According to the regulations and in compliance with general rules of work with radioactivity, radiopharmaceuticals should only be prepared/manufactured under special conditions, using special areas and special equipment and applying special procedures (e.g. sterilisation, disinfection, aseptic work). Also, there are special procedures for cleaning and maintenance. Sometimes the requirements for the product safety clash with those for the safety of the personnel; several examples of solutions pertaining to these cases are given in the lecture. Also, the specific role of cyclotron radiopharmaceuticals is discussed.

A project of 81Rb production and 81Rb/81mKr generator manufacturing is described. 81Rb nuclide is produced on U-120M cyclotron via Kr(p, 2n)Rb reaction using pressurised gaseous target. Generator of a “dry” type is based on the sorption of 81Rb on an ion-exchange paper from which the daughter 81mKr is eluted by air. Parameters of targetry and generator assembly are given. Generator which will be manufactured under pharmaceutical “clean” conditions is intended for lung ventilation studies in nuclear medicine.

Introduction The commercial viability of cyclotron-produced 99m Tc as an alternative to generator-produced 99m Tc depends on several factors. These include: production yield, ease of target processing and recycling of 100 Mo, radiochemical purity, specific activity as well as the presence of other radionuclides, particularly various Tc radioisotopes that cannot be separated chemically and will remain in the final clinical preparation. These Tc radionuclidic impurities are derived from nuclear interactions of the accelerated protons with other stable Mo isotopes present in the enriched 100 Mo target. The aim of our study was to determine experimentally the yields of Tc radioisotopes produced from these stable Mo isotopes as a function of incident beam energy in order to predict radionuclidic purity of 99m Tc produced in highly enriched 100 Mo targets of known isotopic composition. Methods Enriched molybdenum targets of 95 Mo, 96 Mo, 97 Mo, 98 Mo and 100 Mo were prepared by pressing powdered metal into an aluminum target support. The thick targets were bombarded with 10 to 24MeV protons using the external beam line of the U-120M cyclotron of the Nuclear Physics Institute, Řež. The thick target yields of 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96m+g Tc and 97m Tc were derived from their activities measured by γ spectrometry using a high purity Ge detector. These data were then used to assess the effect of isotopic composition of highly enriched 100 Mo targets on the radionuclidic purity of 99m Tc as a function of proton beam energy. Estimates were validated by comparison to measured activities of Tc radioisotopes in proton irradiated, highly enriched 100 Mo targets of known isotopic composition. Results The measured thick target yields of 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96m+g Tc and 97m Tc correspond well with recently published values calculated via the EMPIRE-3 code. However, the measured yields are more favourable with regard to achievable radionuclidic purity of 99m Tc. Reliability of the measured thick target yields was demonstrated by comparison of the estimated and measured activities of 94 Tc, 95 Tc, 95m Tc, and 96m+g Tc in highly enriched 100 Mo (99%) targets that showed good agreement, with maximum differences within estimated uncertainties. Radioisotopes 94m Tc and 97m Tc were not detected in the irradiated 100 Mo targets due to their low activities and measurement conditions; on the other hand we detected small amounts of the short-lived positron emitter 93 Tc ( T ½ =2.75h). In addition to 99m Tc and trace amounts of the various Tc isotopes, significant activities of 96 Nb, 97 Nb and 99 Mo were detected in the irradiated 100 Mo targets. Conclusions Radioisotope formation during the proton irradiation of Mo targets prepared from different, enriched stable Mo isotopes provides a useful data base to predict the presence of Tc radionuclidic impurities in 99m Tc derived from proton irradiated 100 Mo targets of known isotopic composition. The longer-lived Tc isotopes including 94 Tc ( T ½ =4.883h), 95 Tc ( T ½ =20.0h), 95m Tc ( T ½ =61 d), 96m+g Tc ( T ½ =4.24 d) and 97m Tc ( T ½ =90 d) are of particular concern since they may affect the dosimetry in clinical applications. Our data demonstrate that cyclotron production of 99m Tc, using highly enriched 100 Mo targets and 19–24MeV incident proton energy, will result in a product of acceptable radionuclidic purity for applications in nuclear medicine.

The energy of the 9.4 keV γ-transition observed in the 83Rb decay was established to be 9405.8(3) eV. This energy value was obtained from photon spectrometry measurements of the differences in the energies of closely spaced lines. The result allows one to determine more precisely the energy of conversion electrons of the 9.4 keV transition, which represent a unique tool for energy calibration of the tritium beta spectrum and systematic measurements in the KATRIN neutrino mass determination experiment.

The isomer 83mKr with its half-life of 1.83 h is an ideal calibration source for a liquid noble gas dark matter experiment like the XENON project. However, the risk of contamination of the detector with traces of the much longer lived mother isotop 83Rb (86.2 d half-life) has to be ruled out. In this work the release of 83Rb atoms from a 1.8 MBq 83Rb source embedded in zeolite beads has been investigated. To do so, a cryogenic trap has been connected to the source for about 10 days, after which it was removed and probed for the strongest 83Rb gamma-rays with an ultra-sensitive Germanium detector. No signal has been found. The corresponding upper limit on the released 83Rb activity means that the investigated type of source can be used in the XENON project and similar low-background experiments as 83mKr generator without a significant risk of contaminating the detector. The measurements also allow to set upper limits on the possible release of the isotopes 84Rb and 86Rb, traces of which were created alongside the production of 83Rb at the Rez cyclotron., Comment: 11 pages, 7 figures, submitted to Journal of Instrumentation

A difficult task with many particle detectors focusing on interactions below ~100 keV is to perform a calibration in the appropriate energy range that adequately probes all regions of the detector. Because detector response can vary greatly in various locations within the device, a spatially uniform calibration is important. We present a new method for calibration of liquid xenon (LXe) detectors, using the short-lived 83m-Kr. This source has transitions at 9.4 and 32.1 keV, and as a noble gas like Xe, it disperses uniformly in all regions of the detector. Even for low source activities, the existence of the two transitions provides a method of identifying the decays that is free of background. We find that at decreasing energies, the LXe light yield increases, while the amount of electric field quenching is diminished. Additionally, we show that if any long-lived radioactive backgrounds are introduced by this method, they will present less than 67E-6 events/kg/day in the next generation of LXe dark matter direct detection searches, 9 pages, 9 figures. Accepted to Review of Scientific Instruments

A new simplified approach for the preparation of 211 At-labelled compounds is presented. The labelling procedure is carried out entirely in a Teflon capillary which also serves as a cryotrap. Two organic astatine compounds were synthesized by this method: 5-[ 211 At]astato-2′-deoxyuridine (AUdR) and N -succinimidyl-4-[ 211 At]astatobenzoate (SAB), starting from their respective stannylated precursors. The first reaction was performed in aqueous solution and the latter in an organic solvent using Iodogen as the oxidant in both cases. Overall radiochemical yields were approximately 75% for AUdR and approximately 70% for SAB.

The separation of krypton and xenon is of particular importance for the field of direct dark matter search with liquid xenon detectors. The intrinsic contamination of the xenon with radioactive (85)Kr makes a significant background for these kinds of low count-rate experiments and has to be removed beforehand. This can be achieved by cryogenic distillation, a technique widely used in industry, using the different vapor pressures of krypton and xenon. In this paper, we present an investigation on the separation performance of a single stage distillation system using a radioactive (83m)Kr-tracer method. The separation characteristics under different operation conditions are determined for very low concentrations of krypton in xenon at the level of (83m)Kr/Xe = 1.9 ⋅ 10(-15), demonstrating, that cryogenic distillation in this regime is working. The observed separation is in agreement with the expectation from the different volatilities of krypton and xenon. This cryogenic distillation station is the first step on the way to a multi-stage cryogenic distillation column for the next generation of direct dark matter experiment XENON1T.