Search Results (18)

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

Background/Objective Pancreatic stellate cells (PSCs) in pancreatic adenocarcinoma (PDAC) are producing extracellular matrix, which promotes the formation of a dense fibrotic microenvironment. This makes PDAC a highly heterogeneous tumor-stroma-driven entity, associated with reduced perfusion, limited oxygen supply, high interstitial fluid pressure, and limited bioavailability of therapeutic agents. Methods In this study, spheroid and tumor xenograft models of human PSCs and PanC-1 cells were characterized radiopharmacologically using a combined positron emission tomography (PET) radiotracer approach. [¹⁸F]FDG, [¹⁸F]FMISO, and [¹⁸F]FAPI-74 were employed to monitor metabolic activity, hypoxic metabolic state, and functional expression of fibroblast activation protein alpha (FAPα), a marker of activated PSCs. Results In vitro, PanC-1 and multi-cellular tumor spheroids demonstrated comparable glucose uptake and hypoxia, whereas FAPα expression was significantly higher in PSC spheroids. In vivo, glucose uptake as well as the transition to hypoxia were comparable in PanC-1 and multi-cellular xenograft models. In mice injected with PSCs, FAPα expression decreased over a period of four weeks post-injection, which was attributed to the successive death of PSCs. In contrast, FAPα expression increased in both PanC-1 and multi-cellular xenograft models over time due to invasion of mouse fibroblasts. Conclusion The presented models are suitable for subsequently characterizing stromal cell-induced metabolic changes in tumors using noninvasive molecular imaging techniques. Full article

The present work promotes and validates the benefits of using niobium instead of Havar^® as the material for the target windows in most routine irradiations in cyclotrons. Calculation of the material activation and measurements of the contamination of the transferred target liquids show major improvements with the use of niobium. Also, the data of the daily routine productions at our production center are presented, proving that Havar^® is not mandatory unless large target currents and/or pressures are required. Full article

Four-dimensional visualization, i.e., three-dimensional space plus time, of fluid flow and its interactions in geological materials using positron emission tomography (PET) requires suitable radiotracers that exhibit the desired physicochemical interactions. ⁷⁶Br is a likely candidate as a conservative tracer in these studies. [⁷⁶Se]CoSe was produced and used as the target material for the production of ⁷⁶Br via the (p,n) reaction at a Cyclone 18/9 cyclotron. ⁷⁶Br was separated from the target by thermochromatographic distillation using a semi-automated system, combining a quartz glass apparatus with a synthesis module. ⁷⁶Br was successfully produced at the cyclotron with a physical yield of 72 MBq/µAh (EOB). The total radiochemical yield of ⁷⁶Br from the irradiated [⁷⁶Se]CoSe target (EOS) was 68.6%. A total of 40 MBq–100 MBq n.c.a. ⁷⁶Br were routinely prepared for PET experiments in 3 mL 20 mM Cl⁻ solution. The spatial resolution of a PET scan with ⁷⁶Br in geological materials was determined to be about 5 mm. The established procedure enables the routine investigation of hydrodynamics by PET techniques in geological materials that strongly sorb commonly used PET tracers such as ¹⁸F. Full article

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. 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

The emerging success of [⁶⁸Ga/¹⁷⁷Lu]Ga/Lu-DOTATATE as a theranostic pair has spurred interest in other isotopes as potential theranostic combinations. Here, we review cobalt-55 and cobalt-58m as a potential theranostic pair. Radionuclidically pure cobalt-55 and cobalt-58m have been produced on small cyclotrons with high molar activity. In vitro, DOTATOC labeled with cobalt has shown greater affinity for SSTR2 than DOTATOC labeled with gallium and yttrium. Similarly, [^58mCo]Co-DOTATATE has shown improved cell-killing capabilities as compared to DOTATATE labeled with either indium-111 or lutetium-177. Finally, PET imaging with an isotope such as cobalt-55 allows for image acquisition at much later timepoints than gallium, allowing for an increased degree of biological clearance of non-bound radiotracer. We discuss the accelerator targetry and radiochemistry used to produce cobalt-55,58m, emphasizing the implications of these techniques to downstream radiotracers being developed for imaging and therapy. Full article

The TERESA (TEstbed for high REpetition-rate Sources of Accelerated particles) target area, recently commissioned with the L3-HAPLS laser at Extreme Light Infrastructure (ELI)-Beamlines, is presented. Its key technological sections (vacuum and control systems, laser parameters and laser beam transport up to the target) are described, along with an overview of the available plasma diagnostics and targetry, tested at relativistic laser intensities. Perspectives of the TERESA laser–plasma experimental area at ELI-Beamlines are briefly discussed. 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

Many medical isotopes can be produced on a small cyclotron. The alignment and profiles of low-energy proton beams from cyclotrons used for medical radioisotope production, such as the TR13 cyclotron at TRIUMF, Canada, cannot be directly quantified during dose delivery with simultaneous constant feedback and sharp spatial resolutions. Doped silica fibers are a potential solution that has been tested at TRIUMF. To measure the effects of irradiation inside an isotope production target, we attached fibers to the outside of an ¹⁸O gas target and measured the light output during irradiation. Different dopants, fiber diameters, and target materials were investigated. It was found that 200 µm diameter Ce- and B-doped fibers produce signals linearly proportional to the beam current. This only deviated when the target was moved such that the beam was steered into the target wall, increasing the production of prompt radiation and causing the beam current to decrease but the fiber signal to increase. With the technique described here, the beam can be monitored on the target, including its steering and its overall alignment with the target. Full article

The production of novel radionuclides is the first step towards the development of new effective radiopharmaceuticals, and the quality thereof directly affects the preclinical and clinical phases. In this review, novel radiometal production for medical applications is briefly elucidated. The production status of the imaging nuclide ⁴⁴Sc and the therapeutic β^--emitter nuclide ¹⁶¹Tb are compared to their more established counterparts, ⁶⁸Ga and ¹⁷⁷Lu according to their targetry, irradiation process, radiochemistry, and quality control aspects. The detailed discussion of these significant issues will help towards the future introduction of these promising radionuclides into drug manufacture for clinical application under Good Manufacturing Practice (GMP). Full article

A significant number of medical radioisotopes use solid, often metallic, parent materials. These materials are deposited on a substrate to facilitate the cooling and handling of the target during placing, irradiation, and processing. The processing requires the transfer of the target to a processing area outside the irradiation area. In this new approach the target is processed at the irradiation site for liquid only transport of the irradiated target material to the processing area. The design features common to higher energy production target systems are included in the target station. The target is inclined at 14 degrees to the beam direction. The system has been designed to accept an incident beam of 15 to 16 mm diameter and a beam power between 2 and 5 kW. Thermal modeling is presented for targets of metals and compounds. A cassette of five or 10 prepared targets is housed at the target station as well as a target dissolution assembly. Only the dissolved target material is transported to the chemistry laboratory so that the design does not require additional irradiation area penetrations. This work presents the design, construction, and modeling details of the assembly. A full performance characterization will be reported after the unit is moved to a cyclotron facility for beam related measurements. Full article

A 3D-printed metal solid target using additive manufacturing process is a cost-effective production solution to complex and intricate target design. The initial proof-of-concept prototype solid target holder was 3D-printed in cast alloy, Al–7Si–0.6Mg (A357). However, given the relatively low thermal conductivity for A357 (κ_max, 160 W/m·K), replication of the solid target holder in sterling silver (SS925) with higher thermal conductivity (κ_max, 361 W/m·K) was investigated. The SS925 target holder enhances the cooling efficiency of the target design, thus achieving higher target current during irradiation. A validation production of ⁶⁴Cu using the 3D-printed SS925 target holder indicated no loss of enriched ⁶⁴Ni from proton bombardment above 80 µA, at 11.5 MeV. Full article

In solid targets for radioisotope production, the parent materials—mostly metallic—are usually attached to a substrate (metal part, often copper or silver) to support it during handling and irradiation and to facilitate liquid or gas cooling to remove the heat generated by the particle beam. This cladding process is most frequently done by electroplating. One of the biggest challenges of preparing solid, high-current, ¹⁰⁰Mo targets is the difficulty of cladding the substrate with molybdenum—metal that cannot be electroplated. A number of cladding techniques are used with varying degrees of complexity, success, and cost. A simple cladding process, especially suitable for the production of radioisotope targets, was developed. The process uses a metal slurry (metal powder and binder) painted on the substrate and heated in a hydrogen atmosphere where the metal is sintered and diffusion-bound to the substrate in a single step. Full article