Search Results (24)

Radioactive contaminations in soil, which originate from nuclear power production, nuclear weapon testing, or uncontrolled release, are of great environmental concern. One of the major fission product contaminants is ⁹⁰Sr, whose high mobility demands a method to track contamination pathways and remediation processes. Positron emission tomography (PET) is a valuable tool for the required studies. As a β⁻/γ-emitter, ⁹⁰Sr is not suitable for PET, which requires β⁺-emitters. As an alternative, ⁸³Sr, with a 12% intensity of β⁺-emission and a half-life of 32.4 h, is an appropriate PET substitute for ⁹⁰Sr. We produced ⁸³Sr with an enriched target of [⁸⁵Rb]RbCl in a ⁸⁵Rb(p,3n)⁸³Sr reaction. The target material was bombarded with 36.22 MeV protons (ø 1.78 µA, 315 min), at a solid target station at the cyclotron U-120M (NPI CAS). The irradiated target (1.5 GBq) was dissolved in water, evaporated to dryness, redissolved in nitric acid, and transferred onto a Sr-selective cartridge (Sr-SpecTM, TRISKEM, France). Following target material wash out, ⁸³Sr elution with water, solvent evaporation, and reformulation (in dilute nitric acid) yielded 1.2 GBq (82% radiochemical extraction efficiency, non-decay-corrected) of an ⁸³Sr-solution. The easy and fast method is able to produce non-carrier-added ⁸³Sr with high radionuclidic purity. Full article

Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from ⁶⁸Ge/⁶⁸Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [⁶⁸Ga]Ga-PSMA-11 and [⁶⁸Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications. Full article

At the Radiopharmaceutical Research Center (CCR) of the Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), we operate a TR-19 cyclotron for radio isotope production. To broaden our spectrum of radioisotopes with applications in nuclear medicine, we add a new external beam line towards a state-of-the-art solid target station. Besides practical experience with the implementation of the Comecer ALCEO metal solid targetry system, a new, more efficient way of tuning the beam onto the target and the design of a dedicated neutron local layered shielding are presented. Full article

On the verge of a theranostic approach to personalised medicine, copper-64 is one of the emerging radioisotopes in nuclear medicine due to its exploitable nuclear and biochemical characteristics. The increased demand for copper-64 for preclinical and clinical studies has prompted the development of production routes. This research aims to compare the (p,n) reaction on nickel-64 solid versus liquid targets and evaluate the effectiveness of [⁶⁴Cu]CuCl₂ solutions prepared by the two routes. As new treatments for neurotensin receptor-overexpressing tumours have developed, copper-64 was used to radiolabel Neurotensin (8-13) and Neuromedin N. High-quality [⁶⁴Cu]CuCl₂ solutions were prepared using ACSI TR-19 and IBA Cyclone Kiube cyclotrons. The radiochemical purity after post-irradiation processing reached 99% (LT) and 99.99% (ST), respectively. The irradiation of a solid target with 11.8 MeV protons and 150 μAh led to 704 ± 84 MBq/μA (17.6 ± 2.1 GBq/batch at EOB). At the end of the purification process (1 h, 90.90% activity yield), the solution for peptide radiolabelling had a radioactive concentration of 1340.4 ± 70.1 MBq/mL (n.d.c.). The irradiation of a liquid target with 16.9 MeV protons and 230 μAh resulted in 3.7 ± 0.2 GBq/batch at EOB, which corresponds to an experimental production yield of 6.89 GBq.cm3/(g.µA)_sat. Benefiting from a shorter purification process (40 min), the activity yielded 90.87%, while the radioactive concentration of the radiolabelling solution was lower (492 MBq/mL, n.d.c.). The [⁶⁴Cu]CuCl₂ solutions were successfully used for the radiolabelling of DOTA-NT(8-13) and DOTA-NN neuropeptides, resulting in a high RCP (>99%) and high molar activity (27.2 and 26.4 GBq/μmol for LT route compared to 45 and 52 GBq/μmol for ST route, respectively). The strong interaction between the [⁶⁴Cu]Cu-DOTA-NT(8-13) and the colon cancerous cell lines HT29 and HCT116 proved that the specificity for NTR had not been altered, as shown by the uptake and retention data. Full article

In the field of nuclear medicine, the β⁺ -emitting ⁴³Sc and β⁻ -emitting ⁴⁷Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, scandium is a group-3 transition metal (like ¹⁷⁷Lu) and exhibits affinity for DOTA-based chelators, which have been studied in depth, making the barrier to implementation lower for ^43/47Sc than for other proposed true theranostics. Before ^43/47Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established and each isotope’s radiolabeling and animal imaging capabilities studied with a widely utilized tracer. As such, a simple means of converting an 18 MeV biomedical cyclotron to support solid targets and produce ⁴³Sc via the ⁴²Ca(d,n)⁴³Sc reaction has been devised, exhibiting reasonable yields. The ^NatTi(γ,p)⁴⁷Sc reaction is also investigated along with the successful implementation of chemical separation and purification methods for ^43/47Sc. The conjugation of ^43/47Sc with PSMA-617 at specific activities of up to 8.94 MBq/nmol and the subsequent imaging of LNCaP-ENZaR tumor xenografts in mouse models with both ^43/47Sc-PSMA-617 are also presented. Full article

Antibody and nanobody-based copper-64 radiopharmaceuticals are increasingly being proposed as theranostic tools in multiple human diseases. While the production of copper-64 using solid targets has been established for many years, its use is limited due to the complexity of solid target systems, which are available in only a few cyclotrons worldwide. In contrast, liquid targets, available in virtually in all cyclotrons, constitute a practical and reliable alternative. In this study, we discuss the production, purification, and radiolabeling of antibodies and nanobodies using copper-64 obtained from both solid and liquid targets. Copper-64 production from solid targets was performed on a TR-19 cyclotron with an energy of 11.7 MeV, while liquid target production was obtained by bombarding a nickel-64 solution using an IBA Cyclone Kiube cyclotron with 16.9 MeV on target. Copper-64 was purified from both solid and liquid targets and used to radiolabel NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab conjugates. Stability studies were conducted on all radioimmunoconjugates in mouse serum, PBS, and DTPA. Irradiation of the solid target yielded 13.5 ± 0.5 GBq with a beam current of 25 ± 1.2 μA and an irradiation time of 6 h. On the other hand, irradiation of the liquid target resulted in 2.8 ± 1.3 GBq at the end of bombardment (EOB) with a beam current of 54.5 ± 7.8 μA and an irradiation time of 4.1 ± 1.3 h. Successful radiolabeling of NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab with copper-64 from both solid and liquid targets was achieved. Specific activities (SA) obtained with the solid target were 0.11, 0.19, and 0.33 MBq/μg for NODAGA-Nb, NOTA-Nb, and DOTA-trastuzumab, respectively. For the liquid target, the corresponding SA values were 0.15, 0.12, and 0.30 MBq/μg. Furthermore, all three radiopharmaceuticals demonstrated stability under the testing conditions. While solid targets have the potential to produce significantly higher activity in a single run, the liquid process offers advantages such as speed, ease of automation, and the feasibility of back-to-back production using a medical cyclotron. In this study, successful radiolabeling of antibodies and nanobodies was achieved using both solid and liquid targets approaches. The radiolabeled compounds exhibited high radiochemical purity and specific activity, rendering them suitable for subsequent in vivo pre-clinical imaging studies. Full article

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 $\mathsf{\mu }$m film onto different substrates is developed. Such configuration for solid target manufacturing has been proposed for the first time. Two $ZnO$ depositions (20–30 $\mathsf{\mu }$m) 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. Full article

Theranostic matched pairs of radionuclides have aroused interest during the last couple of years, and in that sense, copper is one element that has a lot to offer, and although ⁶¹Cu and ⁶⁴Cu are slowly being established as diagnostic radionuclides for PET, the availability of the therapeutic counterpart ⁶⁷Cu plays a key role for further radiopharmaceutical development in the future. Until now, the ⁶⁷Cu shortage has not been solved; however, different production routes are being explored. This project aims at the production of no-carrier-added ⁶⁷Cu with high radionuclidic purity with a medical 30MeV compact cyclotron via the ⁷⁰Zn(p,α)⁶⁷Cu reaction. With this purpose, proton irradiation of electrodeposited ⁷⁰Zn targets was performed followed by two-step radiochemical separation based on solid-phase extraction. Activities of up to 600MBq ⁶⁷Cu at end of bombardment, with radionuclidic purities over 99.5% and apparent molar activities of up to 80MBq/nmol, were quantified. Full article

Designing and implementing various radionuclide production methods guarantees a sustainable supply, which is important for medical use. The use of medical cyclotrons for radiometal production can increase the availability of gallium-68 (⁶⁸Ga) radiopharmaceuticals. Although generators have greatly influenced the demand for ⁶⁸Ga radiopharmaceuticals, the use of medical cyclotrons is currently being explored. The resulting ⁶⁸Ga production is several times higher than obtained from a generator. Moreover, the use of solid targets yields end of purification and end of synthesis (EOS) of up to 194 GBq and 72 GBq, respectively. Furthermore, experiments employing liquid targets have provided promising results, with an EOS of 3 GBq for [⁶⁸Ga]Ga-PSMA-11. However, some processes can be further optimized, specifically purification, to achieve high ⁶⁸Ga recovery and apparent molar activity. In the future, ⁶⁸Ga will probably remain one of the most in-demand radionuclides; however, careful consideration is needed regarding how to reduce the production costs. Thus, this review aimed to discuss the production of ⁶⁸Ga radiopharmaceuticals using Advanced Cyclotron Systems, Inc. (ACSI, Richmond, BC, Canada) Richmond, Canada and GE Healthcare, Wisconsin, USA cyclotrons, its related factors, and regulatory concerns. Full article

Cyclotron-based radionuclides production by using solid targets has become important in the last years due to the growing demand of radiometals, e.g., ⁶⁸Ga, ⁸⁹Zr, ^43/47Sc, and ^52/54Mn. This shifted the focus on solid target management, where the first fundamental step of the radiochemical processing is the target dissolution. Currently, this step is generally performed with commercial or home-made modules separated from the following purification/radiolabelling modules. The aim of this work is the realization of a flexible solid target dissolution system to be easily installed on commercial cassette-based synthesis modules. This would offer a complete target processing and radiopharmaceutical synthesis performable in a single module continuously. The presented solid target dissolution system concept relies on an open-bottomed vial positioned upon a target coin. In particular, the idea is to use the movement mechanism of a syringe pump to position the vial up and down on the target, and to exploit the heater/cooler reactor of the module as a target holder. All the steps can be remotely controlled and are incorporated in the cassette manifold together with the purification and radiolabelling steps. The performance of the device was tested by processing three different irradiated targets under different dissolution conditions. Full article

Magnetron sputtering (MS) is a relatively new deposition technique, which is being considered among the cyclotron solid target (CST) manufacturing options now available, aiming at the medical radioisotopes yield for radiopharmaceutical production. However, the intrinsic high material losses during the deposition process do not permit its use with extremely expensive target materials, such as isotopically enriched metals/oxides. In this study, R&D technology for a new recovering shield is instead proposed to assess the dissipation of target material during the sputtering processes and, thus, an estimate of the material recovery that may be feasible and the related amount. The weight-loss analysis method is used to assess the material losses level inside the chamber during processing. In all tests carried out, a high-purity copper (99.99%) was used as a target material. As a result of this study, the material distribution for both magnetron and diode sputtering depositions can be calculated. The feasibility of the ultra-thick coatings growing, devoted to CST production, is demonstrated. Full article

By using solid targets in medical cyclotrons, it is possible to produce large amounts of ⁶⁸GaCl₃. Purification of Ga³⁺ from metal ion impurities is a critical step, as these metals compete with Ga³⁺ in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting ⁶⁸GaCl₃could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. ⁶⁸GaCl₃ was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The ⁶⁸Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The ⁶⁸GaCl₃eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of ⁶⁸Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis. Full article

A novel active focusing system was developed for enhancing the irradiation performance of the 18 MeV medical cyclotron in operation at the Bern University Hospital in view of the production of non-conventional medical radioisotopes using solid targets. In several cases, such as the production of ${}^{43}$Sc and ${}^{44}$Sc, the beam has to be kept stable within a very small target of about 5 mm diameter. For this purpose, we conceived and realized an apparatus based on a compact focusing and steering magnet system followed by a two-dimensional beam monitoring detector and a specific feedback software that drives the magnet to optimize the beam for a given irradiation set-up. We report on the design, realization and validation beam tests performed using the research beam transfer line of the Bern cyclotron. We demonstrated that the beam spot can be kept on target thanks to the fact that the system automatically reacts to perturbations. Compactness is one of the key features of this system, allowing its use in accelerator facilities with limited space, such as medical cyclotrons for radioisotope production. Full article

⁴⁴Sc has favorable properties for cancer diagnosis using Positron Emission Tomography (PET) making it a promising candidate for application in nuclear medicine. The implementation of its production with existing compact medical cyclotrons would mean the next essential milestone in the development of this radionuclide. While the production and application of ⁴⁴Sc has been comprehensively investigated, the development of specific targetry and irradiation methods is of paramount importance. As a result, the target was optimized for the ⁴⁴Ca(p,n)⁴⁴Sc nuclear reaction using CaO instead of CaCO₃, ensuring decrease in target radioactive degassing during irradiation and increased radionuclidic yield. Irradiations were performed at the research cyclotron at the Paul Scherrer Institute (~11 MeV, 50 µA, 90 min) and the medical cyclotron at the University of Bern (~13 MeV, 10 µA, 240 min), with yields varying from 200 MBq to 16 GBq. The development of targetry, chemical separation as well as the practical issues and implications of irradiations, are analyzed and discussed. As a proof-of-concept study, the ⁴⁴Sc produced at the medical cyclotron was used for a preclinical study using a previously developed albumin-binding prostate-specific membrane antigen (PSMA) ligand. This work demonstrates the feasibility to produce ⁴⁴Sc with high yields and radionuclidic purity using a medical cyclotron, equipped with a commercial solid target station. Full article

Magnetron sputtering is proposed here as an innovative method for the deposition of a material layer onto an appropriate backing plate for cyclotron solid targets aimed at medical radioisotopes production. In this study, a method to deposit thick, high-density, high-thickness-uniformity, and stress-free films of high adherence to the backing was developed by optimizing the fundamental deposition parameters: sputtering gas pressure, substrate temperature, and using a multilayer deposition mode, as well. This method was proposed to realize Mo-100 and Y-nat solid targets for biomedical cyclotron production of Tc-99m and Zr-89 radionuclides, respectively. The combination of all three optimized sputtering parameters (i.e., 1.63 × 10⁻² mbar Ar pressure, 500 °C substrate temperature, and the multilayer mode) allowed us to achieve deposition thickness as high as 100 µm for Mo targets. The 50/70-µm-thick Y targets were instead realized by optimizing the sputtering pressure only (1.36 × 10⁻² mbar Ar pressure), without making use of additional substrate heating. These optimized deposition parameters allowed for the production of targets by using different backing materials (e.g., Mo onto copper, sapphire, and synthetic diamond; and Y onto a niobium backing). All target types tested were able to sustain a power density as high as 1 kW/cm² provided by the proton beam of medical cyclotrons (15.6 MeV for Mo targets and 12.7 MeV for Y targets at up to a 70-µA proton beam current). Both short- and long-time irradiation tests, closer to the real production, have been realized. Full article