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This document is a summary of responses received from the public known European industrial manufacturing and research institution and clinical facility representatives. The responses were given to the PRISMAP Consortium questionnaire disseminated in January-August 2022, approaching radionuclides and radiopharmaceuticalmanufacturers, research institutions and clinical end users in nuclear medicine, with the aim to identify potential stakeholders in the industrial and clinical communities interested by a coordinated approach in Europe such as PRISMAP. The summary from PRISMAP questionnaire stratifies the feedback from 114 respondents: radionuclide and radiopharmaceutical producers, research facilities and preclinical/clinical end users. In addition, it gives an insight into the location and capabilities of the main isotope-producing cyclotron facilities, many of which are known from the IAEA cyclotron database [2]). The questionnaire was offered with an opportunity to make new research and international collaboration partners, where all parties could benefit from harmonised supply and legislation procedures, expanding network and distribution routes, and subsequently gain visibility within the PRISMAP User Forum map atwww.prismap.eu. The questionnaire was focused on the radionuclide use in medicine with emphasis on future needs for specific radionuclides and possible research developments with awareness of legislation, logistics and involved personnel education challenges and future perspectives.

A novel production system based on the Isotope Separation On-Line (ISOL) method is being developed to produce intense mass separated 11C beams for PET-aided hadron therapy. In this work, we present a systematic study of the target that was developed for optimized 11C beam production. A solid boron nitride target (BN) with approximately 21% open porosity was manufactured by spark plasma sintering to provide maximized in-target production yield with enhanced isotope release properties. Operational limitations with respect to high temperatures and oxidizing atmospheres were studied, revealing that the BN target can withstand temperatures up to 1500 °C and can be operated with a controlled O2 leak, providing O2 potentials up to −300 kJ/mol, measured at 1000 °C.

The European Physical Society Conference on High Energy Physics, Online conference, jointly organized by Universität Hamburg and the research center DESY; he European Physical Society Conference on High Energy Physics (EPS-HEP2021) 398, 4 pp. (2022). doi:10.22323/1.398.0211, Published by Sissa Medialab Trieste, Italy

CERN-MEDICIS is an off-line isotope separator facility for the extraction of radioisotopes from irradiated targets of interest to medical applications. The beamline, between the ion source and the collection chamber, consists of ion extraction and focusing elements, and a dipole magnet mass spectrometer recovered from the LISOL facility in Louvain-la-Neuve. The latter has been modified for compatibility with MEDICIS, including the installation of a window for injecting laser light into the ion source for resonance photo-ionization. Ion beam optics and magnetic field modeling using SIMION and OPERA respectively were performed for the design and characterization of the beamline. The individual components and their optimal configuration in terms of ion beam extraction, mass separation, and ion transport efficiency is described, along with details of the commissioning and initial performance assessment with stable ion beams. ispartof: Frontiers In Medicine vol:8 ispartof: location:Switzerland status: published

The use of radioactivity in medicine has been developed over a century. The discovery of radioisotopes and their interactions with living cells and tissue has led to the emergence of new diagnostic and therapeutic modalities. The CERN-MEDICIS infrastructure, recently inaugurated at the European Center for Nuclear Research (CERN), provides a wide range of radioisotopes of interest for diagnosis and treatment in oncology. Our objective is to draw attention to the progress made in nuclear medicine in collaboration with CERN and potential future applications, in particular for the treatment of aggressive tumors such as pancreatic adenocarcinoma, through an extensive review of literature. Fifty seven out of two hundred and ten articles, published between 1997 and 2020, were selected based on relevancy. Meetings were held with a multi-disciplinary team, including specialists in physics, biological engineering, chemistry, oncology and surgery, all actively involved in the CERN-MEDICIS project. In summary, new diagnostic, and therapeutic modalities are emerging for the treatment of pancreatic adenocarcinoma. Targeted radiotherapy or brachytherapy could be combined with existing therapies to improve the quality of life and survival of these patients. Many studies are still in the pre-clinical stage but open new paths for patients with poor prognosis.

A porous pre-sintered hexagonal boron nitride powder compact was recently developed as target for the production of intense 11C beams for Positron Emission Tomography-aided hadron therapy. In a previous study, this target has been characterized regarding its operational limitations. In this work, microstructural characterization with respect to the target's grain size, porosity and pore structure, and a dedicated fractional release study from activated targets, i.e. how much 11C is extracted by a short heat treatment, is presented. Corresponding results include an average grain size of approximately 1.7(1) μm, total and open porosity of 40(5) and 21(7)%, respectively, which is mostly composed of pores with sizes ranging from 120 to 470 nm. From the measured release fraction the order of magnitude of carbon's diffusion coefficient D(1500 °C) = 10−15 − 10−14 cm2 s−1 in porous boron nitride, and a 11C extraction efficiency of about 10% at 1500 °C target temperature were estimated.

$^{175}$Yb is a radionuclide that can be generated by neutron capture on $^{174}$Yb and whose decay properties make it useful for developing therapeutic radiopharmaceuticals. As it happens with many of the emerging radionuclides for medical uses in recent years, its nuclear data were determined decades ago and are not thoroughly documented nor accurate enough for metrological purposes. The last documented reference for the $^{175}$Yb half-life value is 4.185(1) days and dates back to 1989, so a redetermination of the value was considered appropriate before standardization at the Institute of Radiation Physics (IRA, Lausanne, Switzerland) primary measurements laboratory. Three independent measurement methods were used to this purpose: reference ionization chamber (CIR, $chambre$ $d'ionization$ $de$ $référence$), CeBr$_{3}$ γ-ray detector with digital electronics and a second CeBr$_{3}$ detector with analog electronics and single-channel analyzer (SCA) counting. The value obtained for the $^{175}$Yb half-life is 4.1615(30) days which shows a 0.56% relative deviation to the last nuclear reference value (ENSDF 2004) and is supported with a detailed calculation of the associated uncertainty.

5 pags., 3 figs., 1 tab. -- Open Access funded by Creative Commons Atribution Licence 4.0, Gamow-Teller β decay is forbidden if the number of nodes in the radial wave functions of the initial and final states is different. This Δn=0 requirement plays a major role in the β decay of heavy neutron-rich nuclei, affecting the nucleosynthesis through the increased half-lives of nuclei on the astrophysical r-process pathway below both Z=50 (for N>82) and Z=82 (for N>126). The level of forbiddenness of the Δn=1ν1g →π0g transition has been investigated from the β decay of the ground state of Hg into the single-proton-hole nucleus Tl in an experiment at the ISOLDE Decay Station. From statistical observational limits on possible γ-ray transitions depopulating the π0g state in Tl, an upper limit of 3.9×10 % was obtained for the probability of this decay, corresponding to log⁡ft>8.8 within a 95% confidence limit. This is the most stringent test of the Δn=0 selection rule to date., Support from the European Union seventh framework through ENSAR contract no. 262010, the Science and Technology Facilities Council through grants ST/P005314/1, ST/L005743/1 and ST/J000051/1 (UK), the MINECO projects FPA2015-64969-P, FPA2015-65035-P and FPA2017-87568-P (Spain), FWO-Vlaanderen (Belgium), GOA/2015/010 (BOF KU Leuven), the Excellence of Science programme (EOS-FWO), and the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (BriX network P7/12) is acknowledged. ZsP acknowledges support by the ExtreMe Matter Institute EMMI at the GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany. PHR and SMJ ac-knowledge support from the UK Department for Business, Energy and Industrial Strategy via the National Measurement Office.

The structure of Po-208 populated through the EC/beta(+) decay of At-208 is investigated using gamma-ray spectroscopy at the ISOLDE Decay Station. The presented level scheme contains 27 new excited states and 43 new transitions, as well as a further 50 previously observed. rays which have been (re)assigned a position. The level scheme is compared to shell model calculations. Through this analysis approximately half of the beta-decay strength of At-208 is found to proceed via allowed decay and half via first-forbidden decay. The first-forbidden transitions predominantly populate core excited states at high excitation energies, which is qualitatively understood using shell model considerations. This mass region provides an excellent testing ground for the competition between allowed and first-forbidden beta-decay calculations, important for the detailed understanding of the nucleosynthesis of heavy elements.

Particle therapy relies on the advantageous dose deposition which permits to highly conform the dose to the target and better spare the surrounding healthy tissues and organs at risk with respect to conventional radiotherapy. In the case of treatments with heavier ions (like carbon ions already clinically used), another advantage is the enhanced radiobiological effectiveness due to high linear energy transfer radiation. These particle therapy advantages are unfortunately not thoroughly exploited due to particle range uncertainties. The possibility to monitor the compliance between the ongoing and prescribed dose distribution is a crucial step toward new optimizations in treatment planning and adaptive therapy. The Positron Emission Tomography (PET) is an established quantitative 3D imaging technique for particle treatment verification and, among the isotopes used for PET imaging, the 11C has gained more attention from the scientific and clinical communities for its application as new radioactive projectile for particle therapy. This is an interesting option clinically because of an enhanced imaging potential, without dosimetry drawbacks; technically, because the stable isotope 12C is successfully already in use in clinics. The MEDICIS-Promed network led an initiative to study the possible technical solutions for the implementation of 11C radioisotopes in an accelerator-based particle therapy center. We present here the result of this study, consisting in a Technical Design Report for a 11C Treatment Facility. The clinical usefulness is reviewed based on existing experimental data, complemented by Monte Carlo simulations using the FLUKA code. The technical analysis starts from reviewing the layout and results of the facilities which produced 11C beams in the past, for testing purposes. It then focuses on the elaboration of the feasible upgrades of an existing 12C particle therapy center, to accommodate the production of 11C beams for therapy. The analysis covers the options to produce the 11C atoms in sufficient amounts (as required for therapy), to ionize them as required by the existing accelerator layouts, to accelerate and transport them to the irradiation rooms. The results of the analysis and the identified challenges define the possible implementation scenario and timeline.

Encouraging results from targeted α-therapy have received significant attention from academia and industry. However, the limited availability of suitable radionuclides has hampered widespread translation and application. In the present review, we discuss the most promising candidates for clinical application and the state of the art of their production and supply. In this review, along with 2 forthcoming reviews on chelation and clinical application of α-emitting radionuclides, The Journal of Nuclear Medicine will provide a comprehensive assessment of the field. ispartof: J Nucl Med vol:62 issue:11 pages:1495-1503 ispartof: location:United States status: published

The CERN-MEDICIS facility aims to produce emerging medical radionuclides for the theranostics approach in nuclear medicine with mass separation of ion beams. To enhance the radioisotope yield and purity of collected samples, the resonance ionization laser ion source MELISSA was constructed, and provided the first laser ions at the facility in 2019. Several operational tests were accomplished to investigate its performance in preparation for the upcoming production of terbium radioisotopes, which are of particular interest for medical applications. © 2020, The Author(s). KU Leuven Horizon 2020: 642889 MEDICIS-PROMED 05P12UMCIA, 05P15UMCIA Open Access funding provided by Projekt DEAL. We would like to acknowledge the help and assistance from the whole MEDICIS collaboration; from CERN-ISOLDE Technical and Physical groups. This research project has been supported by a Marie Skłodowska-Curie Innovative Training Network Fellowship of the European Commission’s Horizon 2020 Programme under contract number 642889 MEDICIS-PROMED; by the German Federal Ministry of Education and Research under the consecutive projects 05P12UMCIA and 05P15UMCIA; by the Research Foundation Flanders FWO (Belgium) and by a KU Leuven START grant.

The β decay of ^{208}Hg into the one-proton hole, one neutron-particle _{81}^{208}Tl_{127} nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z

The goal for the ECHo experiment is the determination of the effective electron neutrino mass by analyzing the electron capture (EC) spectrum of $^{163}$Ho. Metallic magnetic calorimeters enclosing $^{163}$Ho, achieved very good performance to conduct such an experiment. During the first phase of the experiment, ECHo-1k, the detector production and the implantation process of high purity $^{163}$Ho have been optimized. Large detector arrays have been developed, featuring energy resolution below 5eV and activity of about 1Bq per pixel. High statistics and high resolution $^{163}$Ho spectra have been acquired and analyzed in light of new theoretical description of the spectral shape, considering the independently determined Q$_{\mathrm{EC}}$-value, and a dedicated background model. In this contribution, we present preliminary results obtained in the first phase of ECHo. At the same time, we discuss the necessary upgrades towards the second phase of the experiment, ECHo-100k.

The β decay of 207Hg into the single-proton-hole nucleus 207Tl has been studied through γ-ray spectroscopy at the ISOLDE Decay Station (IDS) with the aim of identifying states resulting from coupling of the πs−11/2, πd−13/2, and πh−111/2 shell model orbitals to the collective octupole vibration. Twenty-two states were observed lying between 2.6 and 4.0 MeV, eleven of which were observed for the first time, and 78 new transitions were placed. Two octupole states (s1/2-coupled) are identified and three more states (d3/2-coupled) are tentatively assigned using spin-parity inferences, while further h11/2-coupled states may also have been observed for the first time. Comparisons are made with state-of-the-art large-scale shell model calculations and previous observations made in this region, and systematic underestimation of the energy of the octupole vibrational states is noted. We suggest that in order to resolve the difference in predicted energies for collective and noncollective t=1 states (t is the number of nucleons breaking the 208Pb core), the effect of t=2 mixing may be reduced for octupole-coupled states. The inclusion of mixing with t=0,2,3 excitations is necessary to replicate all t=1 state energies accurately.

6 pags., 6 figs. -- 27th International Nuclear Physics Conference (INPC2019) 29 July - 2 August 2019, Glasgow, UK, The neutron-deficient 115Cs was produced at ISOLDE, CERN by spallation reaction using 1.4 GeV proton on LaC2 target. The exotic decay modes were studied by using a charged particle array (DSSD and pad detectors) and a ¿-detector array (four Clovers) at the ISOLDE decay station (IDS). In this report, results on observed ß-delayed particle emission from 115Cs, a nucleus close to proton drip line, is presented. By measuring the time distribution in the delayed proton spectrum, the half-life of the ground state of 115Cs was extracted. The obtained half-life is in agreement with previous reported value. For the first time, the p-unbound states of 115Xe, obtained by measuring beta-delayed protons from 115Cs is reported., Ushasi Datta acknowledges with thanks to SERB, India for the financial support (travel) for attending and presenting the paper in the conference (INPC2019). Authors of SINP deeply acknowledge the SEND (XI th plan, DAE, India) and IENP/HENPP (XII th plan, DAE, India) project grant. This project has received funding from the European Union’s Horizon 2020 ENSAR2 project under grant agreement no 654002 and the Spanish research council under contract FPA2015-64969-P. The authors (P.Das and A.Bhattacharyya) acknowledge with thanks the financial support provided by the CSIR vide file number 09/489(0111)/2019EMR-I and 09/489(0115)/2019EMR-I respectively.

The Resonance Ionization Laser Ion Source (RILIS) has become an essential feature of many radioactive ion beam facilities worldwide since it offers an unmatched combination of efficiency and selectivity in the production of ion beams of many different chemical elements. In 2019, the laser ion source setup MELISSA is going to be established at the CERN-MEDICIS facility, based on the experience of the workgroup LARISSA of the University Mainz and CERN ISOLDE RILIS team. The purpose is to enhance the capability of the radioactive ion beam supply for end users by optimizing the yield and the purity of the final product. In this article, the blueprint of the laser ion source, as well as the key aspects of its development and operation are presented. The Resonance Ionization Laser Ion Source (RILIS) has become an essential feature of many radioactive ion beamfacilities worldwide since it offers an unmatched combination of efficiency and selectivity in the production ofion beams of many different chemical elements. In 2019, the laser ion source setup MELISSA is going to beestablished at the CERN-MEDICIS facility, based on the experience of the workgroup LARISSA of the UniversityMainz and CERN ISOLDE RILIS team. The purpose is to enhance the capability of the radioactive ion beamsupply for end users by optimizing the yield and the purity of the final product. In this article, the blueprint ofthe laser ion source, as well as the key aspects of its development and operation are presented.

We report the first ionization potentials (IP1) of the heavy actinides, fermium (Fm, atomic number Z = 100), mendelevium (Md, Z = 101), nobelium (No, Z = 102), and lawrencium (Lr, Z = 103), determined using a method based on a surface ionization process coupled to an online mass separation technique in an atom-at-a-time regime. The measured IP1 values agree well with those predicted by state-of-the-art relativistic calculations performed alongside the present measurements. Similar to the well-established behavior for the lanthanides, the IP1 values of the heavy actinides up to No increase with filling up the 5f orbital, while that of Lr is the lowest among the actinides. These results clearly demonstrate that the 5f orbital is fully filled at No with the [Rn]5f(14)7s(2) configuration and that Lr has a weakly bound electron outside the No core. In analogy to the lanthanide series, the present results unequivocally verify that the actinide series ends with Lr.

The European physical journal / C Particles and fields C 79(12), 1026 (2019). doi:10.1140/epjc/s10052-019-7513-x, Published by Springer, Heidelberg

This manuscript describes the production of three targets obtained by implantation of different activities of 7 Be into thin aluminium disks. Two of the produced targets were used to measure the 7 Be(n, p) 7 Li cross section in the energy range of interest for the Big-Bang Nucleosynthesis. A third target was used to measure the cross sections of 7 Be(n, p) 7 Li and 7 Be(n, α ) 7 Li nuclear reactions with cold and thermal neutrons, respectively. This paper describes also the characterization of the first two targets, performed after the neutron irradiation, in terms of implanted 7 Be activities and spatial distributions.

Several experiments on the study of the electron neutrino mass are based on high-statistics measurements of the energy spectrum following electron capture of the radionuclide 163Ho. They rely on the availability of large, radiochemically pure samples of 163Ho. Here, we describe the production, separation, characterization, and sample production within the Electron Capture in Holmium-163 (ECHo) project. 163Ho has been produced by thermal neutron activation of enriched, prepurified 162Er targets in the high flux reactor of the Institut Laue-Langevin, Grenoble, France, in irradiations lasting up to 54 days. Irradiated targets were chemically processed by means of extraction chromatography, which allowed separating the formed Ho from the 162Er target-material and from the main byproducts 170Tm and 171Tm, which are co-produced in GBq amounts. Decontamination factors of >500 for Er and of >105 for Tm and yields of 3.6·1016 and 1.2·1018 atoms of 163Ho were obtained, corresponding to a recovery yield of 95 % of Ho in the chemical separation. The Ho-fraction was characterized by means of γ-ray spectrometry, Inductively-Coupled-Plasma Mass Spectrometry (ICP-MS), Resonance Ionization Mass Spectrometry (RIMS) and Neutron Activation Analysis (NAA). In this process, the thermal neutron capture cross section of 163Ho was measured to σHo-163 to Ho-164m= (23±3) b and σHo-163 to Ho-164g= (156±9) b for the formation of the two isomers of 164Ho. Specific samples were produced for further purification by mass separation to isolate 163Ho from the Ho-isotope mixture, as needed for obtaining the energy spectrum within ECHo. The partial efficiency for this second separation step is (32±5) %.

Ti-foils are currently used as a spallation target material to produce radioisotopes for physics research at the ISOLDE facility at CERN. However, radioisotope production rates often decrease over time due to material degradation from high operation temperatures. Due to enhanced release rates, porous nanomaterials are being studied as spallation target materials for isotope production. TiC is a material with a very high melting point making it an interesting material to replace the Ti-foils. However, in its nanometric form it sinters readily at high temperatures. To overcome this, a new processing route was developed where TiC was co-milled with graphite, carbon black or multi-wall carbon nanotubes in order to hinder the sintering of TiC. The obtained nanocomposite particle sizes, density, specific surface area and porosity were characterized and compared using ANOVA. All carbon allotropes mixed with the TiC, were able to successfully stabilize the nanometric TiC, hindering its sintering up to 1500 °C for 10 h.

This article summarizes the results obtained studying the interaction between polonium and stainless steel 316L in different atmospheres by the thermochromatography method. This issue is particularly important in terms of licensing of the MYRRHA prototype ADS reactor, where highly radiotoxic α-emitting polonium isotopes are produced in lead-bismuth eutectic used as both spallation target material and coolant, while stainless steel 316L is going to be the main structural material. The polonium adsorption enthalpy on stainless steel 316L in inert atmosphere was measured as −147±6 kJ mol−1. The findings obtained using reducing atmospheres show that the affinity of polonium for stainless steel 316L increases with the metallic character of the stainless steel surface. The presence of moisture in inert and reducing atmosphere does not significantly influence the polonium adsorption. Oxidizing atmospheres induce the formation of polonium dioxide which has a stronger interaction with the stainless steel 316L, with an adsorption enthalpy of −225±6 kJ mol−1. A prolonged exposure of the stainless steel to strong oxidants, such as pure oxygen, reduces the metallic character of the stainless steel surface and, consequently, its affinity to the polonium oxide. Furthermore, it was found that in all experiments at least 5 ppm of the total polonium present in the starting material were not retained on the stainless steel 316L surface at all.

The production of selenium ion beams has been investigated at the CERN-ISOLDE facility via two different ionization methods. Whilst molecular selenium (SeCO) beams were produced at ISOLDE since the early 1990s, recent attempts at reliably reproducing these results have so far been unsuccessful. Here we report on tests of a step-wise resonance laser ionization scheme for atomic selenium using the ISOLDE Resonance Ionization Laser Ion Source (RILIS). For stable selenium an ionization efficiency of 1% was achieved. During the first on-line radioisotope production tests, a yield of $ \approx 2.4 \times 10^4$≈2.4×104 ions/μC was measured for 71Se+, using a ZrO2 target with an electron impact ion source. In parallel, an approach for extraction of molecular carbonyl selenide (SeCO) beams was tested. The same ion source and target material were used and a maximum yield of $ \approx 3.6\times 10^5$≈3.6×105 ions/μ C of 71SeCO+ was measured.

The structure of $^{34}$Si was studied through $\gamma$ spectroscopy separately in the $\beta^-$ decays of $^{34}$Mg and $^{34}$Al at the ISOLDE facility of CERN. Different configurations in $^{34}$Si were populated independently from the two recently identified $\beta$-decaying states in $^{34}$Al having spin-parity assignments $J^\pi = 4^-$ dominated by the normal configuration $\pi (d_{5/2})^{-1} \otimes \nu (f_{7/2})$ and $J^\pi = 1^+$ by the intruder configuration $\pi (d_{5/2})^{-1} \otimes \nu (d_{3/2})^{-1}(f_{7/2})^{2}$. The paper reports on spectroscopic properties of $^{34}$Si such as an extended level scheme, spin and parity assignments based on log($ft$) values and $\gamma$-ray branching ratios, absolute $\beta$ feeding intensities and neutron emission probabilities. A total of 11 newly identified levels and 26 transitions were added to the previously known level scheme of $^{34}$Si. Large scale shell-model calculations using the {\sc sdpf-u-mix} interaction, able to treat higher order intruder configurations, are compared with the new results and conclusions are drawn concerning the predictive power of {\sc sdpf-u-mix}, the $N=20$ shell gap, the level of mixing between normal and intruder configurations for the 0$_1^+$, 0$_2^+$ and 2$_1^+$ states and the absence of triaxial deformation in $^{34}$Si.

Four terbium radioisotopes (149, 152, 155, 161Tb) constitute a potential theranostic quartet for cancer treatment but require any derived radiopharmaceutical to be essentially free of impurities. Terbium-155 prepared by proton irradiation and on-line mass separation at the CERN-ISOLDE and CERN-MEDICIS facilities contains radioactive 139Ce16O and also zinc or gold, depending on the catcher foil used. A method using ion-exchange and extraction chromatography resins in two column separation steps has been developed to isolate 155Tb with a chemical yield of ≥95% and radionuclidic purity ≥99.9%. Conversion of terbium into a form suitable for chelation to targeting molecules in diagnostic nuclear medicine is presented. The resulting 155Tb preparations are suitable for the determination of absolute activity, SPECT phantom imaging studies and pre-clinical trials.

Biodistribution studies based on organ harvesting represent the gold standard pre-clinical technique for dose extrapolations. However, sequential imaging is becoming increasingly popular as it allows the extraction of longitudinal data from single animals, and a direct correlation with deterministic radiation effects. We assessed the feasibility of mouse-specific, microPET-based dosimetry of an antibody fragment labeled with the positron emitter 152 Tb [(T 1/2 = 17.5 h, Eβ + mean = 1140 keV (20.3%)]. Image-based absorbed dose estimates were compared with those obtained from the extrapolation to 152 Tb of a classical biodistribution experiment using the same antibody fragment labeled with 111 In. 152 Tb was produced by proton-induced spallation in a tantalum target, followed by mass separation and cation exchange chromatography. The endosialin-targeting scFv78-Fc fusion protein was conjugated with the chelator p-SCN-Bn-CHX-A"-DTPA, followed by labeling with either 152 Tb or 111 In. Micro-PET images of four immunodeficient female mice bearing RD-ES tumor xenografts were acquired 4, 24, and 48 h after the i.v. injection of 152 Tb-CHX-DTPA-scFv78-Fc. After count/activity camera calibration, time-integrated activity coefficients (TIACs) were obtained for the following compartments: heart, lungs, liver, kidneys, intestines, tumor, and whole body, manually segmented on CT. For comparison, radiation dose estimates of 152 Tb-CHX-DTPA-scFv78-Fc were extrapolated from mice dissected 4, 24, 48, and 96 h after the injection of 111 In-CHX-DTPA-scFv78-Fc (3-5 mice per group). Imaging-derived and biodistribution-derived organ TIACs were used as input in the 25 g mouse model of OLINDA/EXM® 2.0, after appropriate mass rescaling. Tumor absorbed doses were obtained using the OLINDA2 sphere model. Finally, the relative percent difference (RD%) between absorbed doses obtained from imaging and biodistribution were calculated. RD% between microPET-based dosimetry and biodistribution-based dose extrapolations were + 12, - 14, and + 17 for the liver, the kidneys, and the tumors, respectively. Compared to biodistribution, the imaging method significantly overestimates the absorbed doses to the heart and the lungs (+ 89 and + 117% dose difference, respectively). MicroPET-based dosimetry of 152 Tb is feasible, and the comparison with organ harvesting resulted in acceptable dose discrepancies for body districts that can be segmented on CT. These encouraging results warrant additional validation using radiolabeled biomolecules with a different biodistribution pattern.

Erbium 169Er is one of the most interesting radiolanthanides for new potential receptor-targeted β− therapy applications due to its low energy β− emissions, very low intensity ɣ rays and the possibility to use 68Ga or 44Sc as companion for diagnostic in a theranostics approach. Currently it can be produced in reactors through the neutron activation of highly enriched 168Er. The low specific activity of the produced carrier-added 169Er is limiting its use for receptor-targeted therapy. Nonetheless it is used for radiosynoviorthesis of small joints. The aim of this work is to develop a new large-scale production method for the supply of very high specific activity 169Er. Highly enriched 168Er target has been irradiated at ILL nuclear reactor and shipped to CERN-MEDICIS. There, the irradiated sample has been mass separated in order to isolate 169Er from the high amount of remaining stable 168Er. The proof of principle for a preclinical dose production has been demonstrated with a collection of ≈17 MBq. The specific activity obtained was ≈240 GBq/mg (≈200 times higher than the product obtained at End of Bombardment – EOB) and the overall separation efficiency was ≈0.2%. Several improvements for the future have been identified and are promising. One of them is the installation of the new laser laboratory at CERN-MEDICIS that will allow to improve the selective ionization of erbium atoms leading to an increase of the efficiency of the method. This method can provide the supply of high specific activity 168Er, first for preclinical studies, and opens also the potential for future large-scale supply. © 2019 This research project has been supported by a Marie Skłodowska-Curie innovative training network fellowship of the European commission’s horizon 2020 program under contract number 642889 MEDICIS-PROMED. This work has been, in part, supported by a grant from the French National Agency for Research called “Investissements d'Avenir”, Equipex Arronax-Plus noANR-11-EQPX-0004 and Labex IRON noANR-11-LABX-18-01.

11 pags., 9 figs., 3 tabs. -- Open Access funded by Creative Commons Atribution Licence 4.0, We report on the development and characterization of the first radioactive boron beams produced by the isotope mass separation online (ISOL) technique at CERN-ISOLDE. Despite the long history of the ISOL technique which exploits thick targets, boron beams have up to now not been available. This is due to the low volatility of elemental boron and its high chemical reactivity which make the definition of an appropriate production target unit difficult. In addition, the short half-lives of all boron radioisotopes complicate tracer release studies. We report here on dedicated offline release studies by neutron capture and alpha detection done with implanted B in prospective target materials, as well as molecule formation and ionization tests, which suggested the use of multiwalled carbon nanotubes (CNT) as target material and injection of sulfur hexafluoride SF to promote volatile boron fluoride formation. Two target units equipped with an arc discharge electron impact ion source VADIS coupled to a water cooled transfer line to retain non-volatile elements and molecules were subsequently tested online. The measured yield of these first B ISOL beams increases in the series BF < BF < B < BF , reaching a maximum yield of 6. 4 × 10 BF ions per μC of protons., This work has been partly supported by the Spanish CICYT through projects, FPA2015-64969-P, and by the European Union by means of the European Commission within its Seventh Framework Program (FP7) via ENSAR (Contract No. 262010). Further, this project has received funding from the European Union Horizon 2020 research and innovation program under grant agreement No. 654002. One of the authors, CS, acknowledges support by the German BMBF via the Gentner program and his local project 05P12RDCIA.

For the first time, the laser resonance photo-ionization technique has been applied inside a FEBIAD-type ion source at an ISOL facility. This was achieved by combining the ISOLDE RILIS with the ISOLDE variant of the FEBIAD ion source (the VADIS) in a series of off-line and on-line tests at CERN. The immediate appli- cations of these developments include the coupling of the RILIS with molten targets at ISOLDE and the introduction of two new modes of FEBIAD operation: an element selective RILIS mode and a RILIS + VADIS mode for increased efficiency compared to VADIS mode operation alone. This functionality has been demonstrated off-line for gallium and barium and on-line for mercury and cadmium. Following this work, the RILIS mode of operation was successfully applied on-line for the study of nuclear ground state and isomer properties of mercury isotopes by in-source resonance ionization laser spectroscopy. The results from the first studies of the new operational modes, of what has been termed the Versatile Arc Discharge and Laser Ion Source (VADLIS), are presented and possible directions for future developments are outlined. publisher: Elsevier articletitle: Blurring the boundaries between ion sources: The application of the RILIS inside a FEBIAD type ion source at ISOLDE journaltitle: Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms articlelink: http://dx.doi.org/10.1016/j.nimb.2016.03.005 content_type: article copyright: © 2016 The Authors. Published by Elsevier B.V. ispartof: Nuclear Instruments & Methods in Physics Research B vol:376 pages:39-45 ispartof: location:Grand Rapids: MI status: published

Hadron therapy was first proposed in 1946 and is by now widespread throughout the world, as witnessed with the design and construction of the CNAO, HIT, PROSCAN and MedAustron treatment centres, among others. The clinical interest in hadron therapy lies in the fact that it delivers precision treatment of tumours, exploiting the characteristic shape (the Bragg peak) of the energy deposition in the tissues for charged hadrons. In particular, carbon ion therapy is found to be biologically more effective, with respect to protons, on certain types of tumours. Following an approach tested at NIRS in Japan [1], carbon ion therapy treatments based on C-12 could be combined or fully replaced with C-11 PET radioactive ions post-accelerated to the same energy. This approach allows providing a beam for treatment and, at the same time, to collect information on the 3D distributions of the implanted ions by PET imaging. The production of C-11 ion beams can be performed using two methods. A first one is based on the production using compact PET cyclotrons with 10-20 MeV protons via N-14(p,alpha)C-11 reactions following an approach developed at the Lawrence Berkeley National Laboratory [2]. A second route exploits spallation reactions F-19(p,X)C-11 and Na-23(p,X)C-11 on a molten fluoride salt target using the ISOL (isotope separation on-line) technique [3]. This approach can be seriously envisaged at CERN-ISOLDE following recent progresses made on C-11(+) production [4] and proven post-acceleration of pure C-10(3/6+) beams in the REX-ISOLDE linac [5]. Part of the required components is operational in radioactive ion beam facilities or commercial medical PET cyclotrons. The driver could be a 70 MeV, 1.2 mA proton commercial cyclotron, which would lead to 8.1 x 10(7) C-11(6+) per spill. This intensity is appropriate using C-11 ions alone for both imaging and treatment. Here we report on the ongoing feasibility studies of such approach, using the Monte Carlo particle transport code FLUKA [6,7] to simulate pristine Bragg Peaks of C-11, in order to compare its performance with C-12, in the context of hadron therapy. (C) 2016 The Authors. Published by Elsevier B.V.