Production Of Medical Radionuclides Research Articles

Chelator-impregnated polydimethylsiloxane beads for the separation of medical radionuclides

Chelator-impregnated resins have been studied earlier for the chemical separation of elements in aqueous solutions, but issues with their chemical stability have limited their use in the separation of (medical) radionuclides from their respective irradiated targets. We developed a polydimethylsiloxane (PDMS)-based chelator-impregnated resin that showed a high chemical stability against leaching. Several different chelators were tested in this study. After impregnation of the PDMS beads with the di-2-ethylhexylphosphoric acid (D2EHPA) chelator, an in-flow separation study with various radionuclides (Y-90, La-140, and Ac-225) was conducted. These three radionuclides have potential use in nuclear medicine and a production route through irradiation of Sr-, Ba-, and Ra-targets respectively, necessitating their chemical separation. The D2EHPA-impregnated beads achieved high adsorption efficiencies of 99.89% ± 0.14%, 99.50% ± 0.10%, and 98.51% ± 0.25%, for Y-90, La-140, and Ac-225, respectively, while co-adsorption of minor amounts (<3%) of the targets were reported. These results, together with the high chemical stability of the PDMS-based resin, highlight the potential of chelator-impregnated resins in the rapidly growing field of (medical) radionuclide production.

Production of Medical Radionuclides in the Center for Radiopharmaceutical Tumor Research—A Status Report

A new Center for Radiopharmaceutical Cancer Research was established at the Helmholtz-Zentrum Dresden-Rossendorf in 2017 to centralize radionuclide and radiopharmaceutical production, as well as enable chemical and biochemical research. Routine production of several radionuclides was put into operation in recent years. We report on the production methods of radiopharmaceutical radionuclides, in particular 11C, 18F, and radio metals like 61Cu, 64Cu, 67Cu, 67Ga, 131Ba, and 133La that are used regularly. In the discussion, we report typical irradiation parameters and achieved saturation yields.

New directions in nuclear data research for accelerator-based production of medical radionuclides

Extensive nuclear data studies have been carried out over the last 30 years in the context of accelerator-based production of radionuclides, especially at energies below 30 MeV, and the achieved database is fairly good. Yet there are some deficiencies or new needs of data. Those needs are generally associated with new emerging clinical applications of radionuclides, e.g. theranostic approach, bimodal imaging, radioimmuno-therapy, etc. This article gives an overview of on-going nuclear data research utilizing charged-particle accelerators in four directions, namely low-energy region, intermediate energy range, use of the α-particle beam, and utilization of fast neutrons generated at accelerators. Wherever possible, a comparison of experimental data with theoretical estimates is presented and evaluated (standardised) data, if available, are also briefly discussed.

CERN-MEDICIS: Operational indicators to support the production of new medical radionuclides by mass-separation

CERN-MEDICIS is an isotope mass separation facility dedicated to biomedical research located in a type A work sector, receiving on average 50% of the 1.4 GeV protons delivered by the Proton Synchrotron Booster (PSB). It was commissioned with Radioactive Ion Beams (RIB’s) in 2017. MEDICIS has operated for the past 5 years in batch mode, with targets irradiated in a station located at the HRS beam dump, and with external sources provided by MEDICIS cyclotrons and nuclear reactors partners, notably during the Long Shutdown (LS2). Additional features of the facility include the MELISSA laser ion source, radiochemistry on implanted radionuclides and an online gamma-ray spectroscopy implantation monitoring. In 2022, we introduced Key Performance Indicators (KPI’s) to monitor the operation of the facility for collected efficiencies, the optimisation of the radiological risks and evaluate impact of possible modifications of the station, paralleling for instance LHC’s integrated luminosity. Defined KPI’s cover aspects in the operation cycle, e.g. planning in CERN schedule, target irradiations, duration of the process, radiological risk mitigation, facility up-time, developments and maintenance. MEDICIS KPI’s can help distinguish which of the operation and infrastructure life cycle requires immediate intervention, developments or consolidation. Those are related to the irradiation stations and irradiation possibilities, the beamlines (parallel collections), target and ion sources (reliability), robot handling and infrastructure, or the separation process itself.

Medical radionuclide research activities at JRC-Geel

A programme to study photon- and neutron-induced reactions of medical interest, as well as accelerator-based methods of medical radionuclide production, has been instituted at JRC-Geel, making use of both existing and new infrastructure. A new electron beamline that can deliver quasi-monoenergetic beams has been commissioned at the GELINA electron linac and will be primarily dedicated to the study of photonuclear reactions and for medical radioisotope production studies via photon irradiation. The recently renewed MONNET 3.5 MV Tandem accelerator provides light ion beams for reactionbased quasi-mono-energetic neutron production and has been used for the study of 99Mo production via neutron irradiation of molybdenum nanoparticles. In this work we present an overview of the medical radionuclide activities at JRCGeel, with particular attention to aspects of the design, development and operational challenges of the new GELINA electron beamline. Some future perspectives of the programme are also discussed.

Cyclotron-based production of innovative medical radionuclides at the INFN-LNL: state of the art and perspective

The production of medical radionuclides is one of the research activities carried out in the framework of the SPES (Selective Production of Exotic Species) project under the completion stage at the Legnaro National Laboratories of the National Institute for Nuclear Physics (INFN-LNL). The heart of SPES is the 70-MeV proton cyclotron having a dual-beam extraction, installed and commissioned in a new building equipped with ancillary laboratories currently under construction. The SPES main goal is the realization of an advanced ISOL (Isotope Separation On-Line) facility to produce re-accelerated exotic ion beams for fundamental nuclear physics studies. The cyclotron double-beam extraction system allows to simultaneously carry out applied research, such as radionuclides production for medicine (SPES-γ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\gamma$$\\end{document}). This paper summarizes the results obtained with the interdisciplinary projects LARAMED (LAboratory of RAdionuclides for MEDicine) and ISOLPHARM (ISOL technique for radioPHARMaceuticals). The first one, based upon the direct activation method, is focused on the production of the radionuclides under the spotlight of the international community (e.g., 99m\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{99m}$$\\end{document}Tc, 67\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{67}$$\\end{document}Cu, 52/51\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{52/51}$$\\end{document}Mn, 47\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{47}$$\\end{document}Sc and Tb isotopes), from the nuclear cross-section measurements up to the preclinical studies. The other one exploits the ISOL technique for the development and production of radioisotopes with high-specific activity, such as 111\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{111}$$\\end{document}Ag, going beyond the state of the art in the field. The most recent SPES-γ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\gamma$$\\end{document} research activities and future perspective are here described, characterized by a consolidated network of collaborations with national and international institutions.

First Results on Zinc Oxide Thick Film Deposition by Inverted Magnetron Sputtering for Cyclotron Solid Targets Production.

The magnetron sputtering technique has been investigated in recent years with ever-growing interest as a verifiable solid target manufacturing technology aimed at the production of medical radionuclides by using low-energy cyclotron accelerators. However, the possible loss of high-cost materials prevents access to work with isotopically enriched metals. The need for expensive materials for the supply of the growing demand for theranostic radionuclides makes the material-saving approach and recovery essential for the radiopharmaceutical field. To overcome the main magnetron sputtering drawback, an alternative configuration is proposed. In this work, an inverted magnetron prototype for the deposition of tens of μm film onto different substrates is developed. Such configuration for solid target manufacturing has been proposed for the first time. Two ZnO depositions (20-30 μm) onto Nb backing were carried out and analysed by SEM (Scanning Electron Microscopy) and XRD (X-ray Diffractogram). Their thermomechanical stability under the proton beam of a medical cyclotron was tested as well. A possible improvement of the prototype and the perspective of its utilisation were discussed.

The significance of nuclear data in the production of radionuclides for theranostic/therapeutic applications

Accurate knowledge of nuclear data are important for the production of radionuclides to be used in medical applications. This study outlines the availability and scarcity of standardized nuclear data for the production of promising medical radionuclides, focusing on the accelerator route. The data are considered for the radionuclides that have the potentials to be used in theranostic applications, i.e., dual-mode imaging and targeted radionuclide therapy. The present status of nuclear data, current trends in nuclear data publication and further requirements for the production of promising theranostic/therapeutic radionuclides by using accelerators are discussed. This work is expected to provide a basic understanding on the accelerator-based production of promising radionuclides in no carrier added form for theranostic medical applications.

Progress of energy-related radiochemistry and radionuclide production in the Republic of Korea

Abstract The field of radiochemistry in the Republic of Korea has expanded greatly over the last three decades to meet the rapid growth of technological demands in various areas such as nuclear energy and nuclear technologies for human health and environmental protection. Major research activities, which were initially centered at the Korea Atomic Energy Research Institute (KAERI), have gradually spread to major universities and the commercial sector. In this review, progress and recent research trends in nuclear and radiochemistry in Korea are summarized. The main research outcomes achieved by KAERI scientists are highlighted, with emphasis on basic actinide chemistry in nuclear fuel cycles, the radioanalytical chemistry of various radionuclides from radioactive waste and the environment, and medical radionuclide production. In addition, recent efforts to promote radiochemical education and future perspectives are briefly outlined.

An overview of nuclear data standardisation work for accelerator-based production of medical radionuclides in Pakistan

Abstract The standardisation of nuclear reaction cross section data is an integral part of optimisation of production routes of medical radionuclides. The production cross sections are available for the reactor and cyclotron produced radionuclides to be used for diagnostics or therapeutic procedures. The types of nuclear data needed, and the sources of their availability are summarized. The method of standardisation of charged-particle data is briefly described. A historical overview of research work in Pakistan in this direction is given. Examples of a few medically important radionuclides, such as 64Cu, 86Y, 89Zr, 103Pd, 186Re, etc., whose data were standardised and evaluated are highlighted. Calculated thick target yields from the recommended data are given. Some new directions in the nuclear data research are outlined.

Cyclotrons Operated for Nuclear Medicine and Radiopharmacy in the German Speaking D-A-CH Countries: An Update on Current Status and Trends.

Cyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine. To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH). Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic "Working Group Radiochemistry and Radiopharmacy" (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN. In total, 42 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 32 of them in Germany, 4 in Austria and 6 in Switzerland. Two thirds of the cyclotrons reported (67%) are operated by universities, university hospitals or research institutions close to a university hospital, less by/in cooperation with industrial partners (29%) or a non-academic clinic/ PET-center (5%). Most of the cyclotrons (88%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging. The data presented provide an academically-updated overview of the medical cyclotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medicine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cyclotron infrastructure in these countries, with a specific focus on organizational aspects.

Upgrade of recommended nuclear cross section data base for production of therapeutic radionuclides

The IAEA Nuclear Data Section has coordinated several actions to setup and improve a database for recommended cross sections and nuclear decay data for various charged-particle reactions that can be used for medical radionuclide production. Some of the earlier evaluations did not provide uncertainties for the recommended cross sections. Updated evaluations with uncertainty quantification for 25 reactions relevant for production of 67Cu, 103Pd, 102mgRh, 114mIn, 125I, 169Yb, 177gLu, 186Re, 192Ir and 210,211At therapeutic radioisotopes are presented. Recommended cross-section data and their uncertainties for production of therapeutic radionuclides are available on the Web page of the IAEA Nuclear Data Section at https://nds.iaea.org/radionuclides and also at the IAEA medical portal https://nds.iaea.org/medportal.

MARIA Reactor Irradiation Technology Capabilities towards Advanced Applications

The MARIA research reactor is designed and operated as a multipurpose nuclear installation, combining material testing, neutron beam experiments, and medical and industrial radionuclide production, including molybdenum-99 (99Mo). Recently, after fuel conversion to LEU and rejuvenation of the staff while maintaining their experience, MARIA has been used to respond to the increased interest of the scientific community in advanced nuclear power studies, both fission and fusion. In this work, we would like to introduce MARIA’ s capabilities in the irradiation technology field and how it can serve future nuclear research worldwide.

Development and Prospect of Theranostic Medical Isotopes and Radiopharmaceuticals in China

Theranostics in nuclear medicine is the combination of radionuclide imaging and internal radiotherapy, so as to realize the visual diagnosis and Precision treatment of diseases. At present, theranostics of nuclear medicine has played an important role in differentiated thyroid cancer, pheochromocytoma, bone metastases, neuroendocrine tumors and prostate cancer. China's medical radionuclides and radionuclides are in short supply, and those are heavily dependent on imports, so there is a bottleneck problem. It is necessary to strengthen the independent production, innovation and research of medical radionuclides and radiopharmaceutics of theranostics, so as to promote theranostics of nuclear medicine to better serve China's clinical practice.

Continuing Nuclear Data Research for Production of Accelerator-Based Novel Radionuclides for Medical Use: A Mini-Review

Nuclear data are important for production and medical application of a radionuclide. This brief review concentrates on nuclear reaction cross-section data. The availability of standardized nuclear data for accelerator-based production of medical radionuclides is outlined. Some new directions in radionuclide applications, for example, theranostic approach, bimodal imaging, and radionuclide targeted therapy, are considered and the status of relevant nuclear data is discussed. The current trends in nuclear data research using accelerators are elaborated. The increasing significance of intermediate energy accelerators in production of therapeutic radionuclides is emphasized.

The Input Window of a Target Station for Operation with Medical Radionuclides

Abstract— The design of an inlet vacuum window, which was developed and manufactured as part of the project of a target station for the production of medical radionuclides, is presented. The calculated data of temperature fields and thermomechanical stresses in the window elements are presented, as well as data on the stress–strain state of the window under the action of the total load (pressure plus uneven heating). Particular attention is paid to the numerical simulation of window cooling by unheated water flows. The “life time” of the window is estimated due to radiation damage to its material. Given the high levels of energy release and induced activity, initiated by protons in the window, as well as its frequent replacement, the AMg6 alloy was selected as the window material.

Comprehensive theoretical studies on stable and radioactive isotopes produced by proton irradiation of titanium target

Natural titanium (natTi) has been suggested to be used as a window or target body in cyclotron-based medical radionuclide production. Therefore, comprehensive theoretical studies regarding impurities that might contribute to proton bombardment of Ti window are of great interest. In this investigation, the TALYS code was employed to calculate nuclear cross-sections of natTi(p,n), natTi(p,2n), natTi(p,α), natTi(p,d) and natTi(n,γ) reactions. The calculations were simulated for proton energies between 1 to 60 MeV. Based on the calculated results, several vanadium (V) radionuclides, e.g. 46,47,48,49,50V were predicted to be generated from natTi(p,n) reaction, whereas vanadium (V) radionuclides, namely 45,46,47,48,49V could be produced from natTi(p,2n) reaction. Some scandium radionuclides, e.g. 43,44,46,47Sccould be resulted from natTi(p,α) reaction, while stable 45Sc isotope was also predicted from this reaction. For natTi(p,d) reaction, 45Ti radionuclide was expected to be generated, while other stable 46,47, 48,49,50Ti atoms could be created as a result of this nuclear reaction. In addition, stable isotope 46Sc was expected to be produced from 46Ti(p,2p)45Sc reaction, while 46,47,48,49Sc radionuclides were foreseen from 47,48,49,50Ti(p,2p) reaction. In the event of secondary neutrons were reflected back and hit the natTi target, several stable 47, 48,49,50Ti atoms were predicted to be produced, whereas short-lived 51Ti radioisotope was expected to rise from 46Ti(p,d)45Ti reaction. This theoretical data could be useful for future radionuclide production should natTi is used as a target window instead of Havar.

Influence of the microstructure on the diffusion barrier performance of Nb-based coatings for cyclotron targets

The number of medical procedures involving the use of cyclotron-produced radionuclides is constantly growing year by year. The design and construction of the cyclotron targets appropriate for the production of the radionuclides of interest are the most challenging issues. The cyclotron targets for the medical radionuclide production suffer from two main corrosion problems: the corrosion due to proton-irradiated water and liquid metal embrittlement. The design of the target for radionuclide production limits the ability to select an ideal material that meets all of the following requirements: machinability or ease of construction, high melting temperature, high thermal exchange performance, excellent chemical inertness, etc. The use of thermally and mechanically suitable substrate materials protected by chemically resistant coatings can be a good compromise. These two corrosion problems can be attributed to the mechanism of diffusion by the aggressive particles through the protective coating. In this research, niobium has been chosen as the principal material for the design of thin film protective coatings. The coating microstructure was correlated to specific deposition parameters to provide chemical resistance to both proton-irradiated water corrosion and liquid metal embrittlement. Film densification and amorphization were pursued to achieve niobium-based thin films efficient as diffusion barriers to proton-irradiated water and liquid metal. The most important conclusions were that the performance of thin films as diffusion barriers varied dramatically based on various deposition parameters and deposition technologies. Among the configurations studied, only three are acceptable as anticorrosion coatings: niobium deposited on axis with unbalanced magnetron sputtering, niobium coated at a high sputtering rate and on a water-cooled sample holder, and the niobium-titanium alloy sputtered at a low argon pressure.

Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide 47Sc

BackgroundIn molecular imaging and nuclear medicine, theranostic agents that integrate radionuclide pairs are successfully being used for individualized care, which has led to rapidly growing interest in their continued development. These compounds, which are radiolabeled with one radionuclide for imaging and a chemically identical or similar radionuclide for therapy, may improve patient-specific treatment and outcomes by matching the properties of different radionuclides with a targeting vector for a particular tumor type. One proposed theranostic radionuclide is scandium-47 (47Sc, T1/2 = 3.35 days), which can be used for targeted radiotherapy and may be paired with the positron emitting radionuclides, 43Sc (T1/2 = 3.89 h) and 44Sc (T1/2 = 3.97 h) for imaging. The aim of this study was to investigate the photonuclear production of 47Sc via the 48Ti(γ,p)47Sc reaction using an electron linear accelerator (eLINAC), separation and purification of 47Sc, the radiolabeling of somatostatin receptor-targeting peptide DOTATOC with 47Sc, and in vitro receptor-mediated binding of [47Sc]Sc-DOTATOC in AR42J somatostatin receptor subtype two (SSTR2) expressing rat pancreatic tumor cells.ResultsThe rate of 47Sc production in a stack of natural titanium foils (n = 39) was 8 × 107 Bq/mA·h (n = 3). Irradiated target foils were dissolved in 2.0 M H2SO4 under reflux. After dissolution, trivalent 47Sc ions were separated from natural Ti using AG MP-50 cation exchange resin. The recovered 47Sc was then purified using CHELEX 100 ion exchange resin. The average decay-corrected two-step 47Sc recovery (n = 9) was (77 ± 7)%. A radiolabeling yield of > 99.9% of [47Sc]Sc-DOTATOC (0.384 mg in 0.3 mL) was achieved using 1.7 MBq of 47Sc. Blocking studies using Octreotide illustrated receptor-mediated uptake of [47Sc]Sc-DOTATOC in AR42J cells.Conclusions47Sc can be produced via the 48Ti(γ,p)47Sc reaction and separated from natural Ti targets with a yield and radiochemical purity suitable for radiolabeling of peptides for in vitro studies. The data in this work supports the potential use of eLINACs for studies of photonuclear production of medical radionuclides and the future development of high-intensity eLINAC facilities capable of producing relevant quantities of carrier-free radionuclides currently inaccessible via routine production pathways or limited due to costly enriched targets.

Recommended nuclear data for medical radioisotope production: diagnostic positron emitters

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 Padé fits to selected and corrected experimental data, and integral thick target yields were subsequently deduced. Uncertainties in the fitted results were estimated via a Padé 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.