Search Results (16)

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

Combining standard surgical procedures with personalized chemotherapy and the continuous monitoring of cancer progression is necessary for effective NSCLC treatment. In this study, we developed liposomal nanoparticles as theranostic agents capable of simultaneous therapy for and imaging of target cancer cells. Copper-64 (⁶⁴Cu), with a clinically practical half-life (t_1/2 = 12.7 h) and decay properties, was selected as the radioisotope for molecular PET imaging. An anti-epidermal growth factor receptor (anti-EGFR) antibody was used to achieve target-specific delivery. Simultaneously, the chemotherapeutic agent doxorubicin (Dox) was encapsulated within the liposomes using a pH-gradient method. The conjugates of ⁶⁴Cu-labeled and anti-EGFR antibody-conjugated micelles were inserted into the doxorubicin-encapsulating liposomes via a post-insertion procedure (⁶⁴Cu-Dox-immunoliposomes). We evaluated the size and zeta-potential of the liposomes and analyzed target-specific cell binding and cytotoxicity in EGFR-positive cell lines. Then, we analyzed the specific therapeutic effect and PET imaging of the ⁶⁴Cu-Dox-immunoliposomes with the A549 xenograft mouse model. In vivo therapeutic experiments on the mouse models demonstrated that the doxorubicin-containing ⁶⁴Cu-immunoliposomes effectively inhibited tumor growth. Moreover, the ⁶⁴Cu-immunoliposomes provided superior in vivo PET images of the tumors compared to the untargeted liposomes. We suggest that nanoparticles will be the potential platform for cancer treatment as a widely applicable theranostic system. Full article

Angiogenesis plays a crucial role in tumour progression and metastatic spread; therefore, the development of specific vectors targeting angiogenesis has attracted the attention of several researchers. Since angiogenesis-associated aminopeptidase N (APN/CD13) is highly expressed on the surface of activated endothelial cells of new blood vessels and a wide range of tumour cells, it holds great promise for imaging and therapy in the field of cancer medicine. The selective binding capability of asparagine-glycine-arginine (NGR) motif containing molecules to APN/CD13 makes radiolabelled NGR peptides promising radiopharmaceuticals for the non-invasive, real-time imaging of APN/CD13 overexpressing malignancies at the molecular level. Preclinical small animal model systems are major keystones for the evaluation of the in vivo imaging behaviour of radiolabelled NGR derivatives. Based on existing literature data, several positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radioisotopes have been applied so far for the labelling of tumour vasculature homing NGR sequences such as Gallium-68 (⁶⁸Ga), Copper-64 (⁶⁴Cu), Technetium-99m (^99mTc), Lutetium-177 (¹⁷⁷Lu), Rhenium-188 (¹⁸⁸Re), or Bismuth-213 (²¹³Bi). Herein, a comprehensive overview is provided of the recent preclinical experiences with radiolabelled imaging probes targeting angiogenesis. Full article

In the present paper, an investigation on the natural and anthropic radioactivity and heavy metals content in a basalt aggregate for concrete from Sicily, Southern Italy, was performed as a case study. In particular, the evaluation of the specific activity of radium-226, thorium-232, potassium-40 and caesium-137 radionuclides was performed by using High-Purity Germanium (HPGe) γ-ray spectrometry, together with the estimation of several indexes developed to evaluate the radiological risk for the population related to radiation exposure, i.e., the alpha index (I_α), the radium equivalent activity (Ra_eq), the absorbed γ-dose rate (D) and the annual effective dose equivalent outdoor (AEDE_out) and indoor (AEDE_in). Moreover, measurements of the average heavy metals (arsenic, cadmium, copper, mercury, nickel, lead, antimony, thallium and zinc) concentrations in the analyzed sample were performed by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Furthermore, with the aim to investigate any possible chemical pollution, the Enrichment Factor (EF), Geo-accumulation Index (I_geo), Contamination Factor (CF) and Pollution Load Index (PLI) were assessed. Finally, the identification of the source of the aforementioned radioisotopes of natural origin was carried out by X-ray diffraction (XRD), thus identifying the major mineralogical phases present in the investigated basalt aggregate for concrete. Full article

Copper radioisotopes are generally employed for cancer imaging and therapy when firmly coordinated via a chelating agent coupled to a tumor-seeking vector. However, the biologically triggered Cu²⁺-Cu⁺ redox switching may constrain the in vivo integrity of the resulting complex, leading to demetallation processes. This unsought pathway is expected to be hindered by chelators bearing N, O, and S donors which appropriately complements the borderline-hard and soft nature of Cu²⁺ and Cu⁺. In this work, the labelling performances of a series of S-rich polyazamacrocyclic chelators with [⁶⁴Cu]Cu²⁺ and the stability of the [⁶⁴Cu]Cu-complexes thereof were evaluated. Among the chelators considered, the best results were obtained with 1,7-bis [2-(methylsulfanyl)ethyl]-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S). DO2A2S was labelled at high molar activities in mild reaction conditions, and its [⁶⁴Cu]Cu²⁺ complex showed excellent integrity in human serum over 24 h. Biodistribution studies in BALB/c nude mice performed with [⁶⁴Cu][Cu(DO2A2S)] revealed a behavior similar to other [⁶⁴Cu]Cu-labelled cyclen derivatives characterized by high liver and kidney uptake, which could either be ascribed to transchelation phenomena or metabolic processing of the intact complex. Full article

PET imaging has gained significant momentum in the last few years, especially in the area of oncology, with an increasing focus on metal radioisotopes owing to their versatile chemistry and favourable physical properties. Copper-61 (t_1/2 = 3.33 h, 61% β⁺, E_max = 1.216 MeV) provides unique advantages versus the current clinical standard (i.e., gallium-68) even though, until now, no clinical amounts of ⁶¹Cu-based radiopharmaceuticals, other than thiosemicarbazone-based molecules, have been produced. This study aimed to establish a routine production, using a standard medical cyclotron, for a series of widely used somatostatin analogues, currently labelled with gallium-68, that could benefit from the improved characteristics of copper-61. We describe two possible routes to produce the radiopharmaceutical precursor, either from natural zinc or enriched zinc-64 liquid targets and further synthesis of [⁶¹Cu]Cu-DOTA-NOC, [⁶¹Cu]Cu-DOTA-TOC and [⁶¹Cu]Cu-DOTA-TATE with a fully automated GMP-compliant process. The production from enriched targets leads to twice the amount of activity (3.28 ± 0.41 GBq vs. 1.84 ± 0.24 GBq at EOB) and higher radionuclidic purity (99.97% vs. 98.49% at EOB). Our results demonstrate, for the first time, that clinical doses of ⁶¹Cu-based radiopharmaceuticals can easily be obtained in centres with a typical biomedical cyclotron optimised to produce ¹⁸F-based radiopharmaceuticals. Full article

Prostate-specific membrane antigen (PSMA) is an ideal target for the diagnosis and treatment of prostate cancer. Due to the short half-life in blood, small molecules/peptides are rapidly cleared by the circulatory system. Prolonging the half-life of PSMA probes has been considered as an effective strategy to improve the tumor detection. Herein, we reported a ⁶⁴Cu-labeled PSMA tracer conjugating with maleimidopropionic acid (MPA), ⁶⁴Cu-PSMA-CM, which showed an excellent ability to detect PSMA-overexpressing tumors in delayed time. Cell experiments in PSMA-positive 22Rv1 cells, human serum albumin binding affinity, and micro-PET imaging studies in 22Rv1 model were performed to investigate the albumin binding capacity and PSMA specificity. Comparisons with ⁶⁴Cu-PSMA-BCH were performed to explore the influence of MPA on the biological properties. ⁶⁴Cu-PSMA-CM could be quickly prepared within 30 min. The uptake of ⁶⁴Cu-PSMA-CM in 22Rv1 cells increased over time and it could bind to HSA with a high protein binding ratio (67.8 ± 1.5%). When compared to ⁶⁴Cu-PSMA-BCH, ⁶⁴Cu-PSMA-CM demonstrated higher and prolonged accumulation in 22Rv1 tumors, contributing to high tumor-to-organ ratios. These results showed that ⁶⁴Cu-PSMA-CM was PSMA specific with a higher tumor uptake, which demonstrated that MPA is an optional strategy for improving the radioactivity concentration in PSMA-expressing tumors and for developing the ligands for PSMA radioligand therapy. Full article

In this work, the radioisotope ⁶⁴Cu was obtained from copper (II) chloride dihydrate in a nuclear research reactor by neutron capture, (⁶³Cu(n,γ)⁶⁴Cu), and incorporated into boron nitride nanotubes (BNNTs) using a solvothermal process. The produced ⁶⁴Cu-BNNTs were analyzed by TEM, MEV, FTIR, XDR, XPS and gamma spectrometry, with which it was possible to observe the formation of⁶⁴Cu nanoparticles, with sizes of up to 16 nm, distributed through nanotubes. The synthesized of ⁶⁴Cu nanostructures showed a pure photoemission peak of 511 keV, which is characteristic of gamma radiation. This type of emission is desirable for Photon Emission Tomography (PET scan) image acquisition, as well as its use in several cancer treatments. Thus, ⁶⁴Cu-BNNTs present an excellent alternative as theranostic nanomaterials that can be used in diagnosis and therapy by different techniques used in nuclear medicine. 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

Double beta decay is a very rare nuclear process and, therefore, experiments intended to detect it must be operated deep underground and in ultra-low background conditions. Long-lived radioisotopes produced by the previous exposure of materials to cosmic rays on the Earth’s surface or even underground can become problematic for the required sensitivity. Here, the studies developed to quantify and reduce the activation yields in detectors and materials used in the set-up of these experiments will be reviewed, considering target materials like germanium, tellurium and xenon together with other ones commonly used like copper, lead, stainless steel or argon. Calculations following very different approaches and measurements from irradiation experiments using beams or directly cosmic rays will be considered for relevant radioisotopes. The effect of cosmogenic activation in present and future double beta decay projects based on different types of detectors will be analyzed too. 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

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

The ISOLPHARM (ISOL technique for radioPHARMaceuticals) project is dedicated to the development of high purity radiopharmaceuticals exploiting the radionuclides producible with the future Selective Production of Exotic Species (SPES) Isotope Separation On-Line (ISOL) facility at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (INFN-LNL). At SPES, a proton beam (up to 70 MeV) extracted from a cyclotron will directly impinge a primary target, where the produced isotopes are released thanks to the high working temperatures (2000 °C), ionized, extracted and accelerated, and finally, after mass separation, only the desired nuclei are collected on a secondary target, free from isotopic contaminants that decrease their specific activity. A case study for such project is the evaluation of the feasibility of the ISOL production of ⁶⁴Cu and ⁶⁷Cu using a zirconium germanide target, currently under development. The producible activities of ⁶⁴Cu and ⁶⁷Cu were calculated by means of the Monte Carlo code FLUKA, whereas dedicated off-line tests with stable beams were performed at LNL to evaluate the capability to ionize and recover isotopically pure copper. Full article

The study of ore minerals is rapidly transforming due to an explosion of new micro- and nano-analytical technologies. These advanced microbeam techniques can expose the physical and chemical character of ore minerals at ever-better spatial resolution and analytical precision. The insights that can be obtained from ten of today’s most important, or emerging, techniques and methodologies are reviewed: laser-ablation inductively-coupled plasma mass spectrometry; focussed ion beam-scanning electron microscopy; high-angle annular dark field scanning transmission electron microscopy; electron back-scatter diffraction; synchrotron X-ray fluorescence mapping; automated mineral analysis (Quantitative Evaluation of Mineralogy via Scanning Electron Microscopy and Mineral Liberation Analysis); nanoscale secondary ion mass spectrometry; atom probe tomography; radioisotope geochronology using ore minerals; and, non-traditional stable isotopes. Many of these technical advances cut across conceptual boundaries between mineralogy and geochemistry and require an in-depth knowledge of the material that is being analysed. These technological advances are accompanied by changing approaches to ore mineralogy: the increased focus on trace element distributions; the challenges offered by nanoscale characterisation; and the recognition of the critical petrogenetic information in gangue minerals, and, thus the need to for a holistic approach to the characterization of mineral assemblages. Using original examples, with an emphasis on iron oxide-copper-gold deposits, we show how increased analytical capabilities, particularly imaging and chemical mapping at the nanoscale, offer the potential to resolve outstanding questions in ore mineralogy. Broad regional or deposit-scale genetic models can be validated or refuted by careful analysis at the smallest scales of observation. As the volume of information at different scales of observation expands, the level of complexity that is revealed will increase, in turn generating additional research questions. Topics that are likely to be a focus of breakthrough research over the coming decades include, understanding atomic-scale distributions of metals and the role of nanoparticles, as well how minerals adapt, at the lattice-scale, to changing physicochemical conditions. Most importantly, the complementary use of advanced microbeam techniques allows for information of different types and levels of quantification on the same materials to be correlated. Full article