47Sc Production Research Articles

Cross section measurements for the production of 49,51Cr and 47Sc from proton irradiation of natural vanadium up to 24 MeV

Scandium-47 is a promising radionuclide for targeted radiotherapy and is also an elementally matched therapeutic partner to 43Sc and 44Sc, which are suitable for Positron Emission Tomography. The predominantly reported routes for the production of 47Sc employ expensive enriched titanium or calcium targets to achieve high radionuclidic purity. This study reports measurements of the excitation function of the natV(p,x)47Sc reaction at proton energies of 18–24 MeV to optimize bombardment parameters for the production of 47Sc using this promising approach. The cross-sections reported here demonstrate that irradiation of vanadium targets can produce >99% radionuclidically pure 47Sc with a proton energy of 24 MeV, albeit at modest yields.

Proton-induced reactions for 47Sc (and 46Sc) production: new nuclear cross section measurements on enriched titanium targets

47Sc is a theranostic radionuclide under the spotlight of the scientific community thanks to its potential for SPECT imaging and therapeutic applications. This work presents the recent measurements of proton-induced nuclear reaction cross-sections aimed at 47Sc production using enriched 48Ti, 49Ti and 50Ti targets from 23 up to 70 MeV. Since the co-production of contaminant isotopes is a key issue, and 46Sc is the main one having a longer half-life than 47Sc, the 48/49/50Ti(p,x)47Sc and 46Sc cross sections are presented and compared with the scarce literature data and TALYS estimations.

Optimized simulations of 50Ti(p,α) and 49Ti(d,α) reactions for hospital-cyclotron production of 47Sc

The production of 47Sc, a promising radioisotope for targeted radionuclide therapy, by means of hospital-cyclotron reactions is investigated. Two possible routes are considered: the proton-induced reaction on enriched 50Ti targets and the deuteron-induced reaction on enriched 49Ti targets. The cross sections of the reactions are calculated using the TALYS code with optimized parameters and compared with the available experimental data. The optimal energy ranges for the production of 47Sc are determined by taking into account the thick-target yields and the purity of the product. The results show that both reactions can provide high yields and high purity of 47Sc. The feasibility of producing 47Sc with a hospital cyclotron is demonstrated by performing realistic simulations of the irradiation for both 50Ti(p,α) and 49Ti(d,α) reactions.

Nuclear Cross-Section of Proton-Induced Reactions on Enriched 48Ti Targets for the Production of Theranostic 47Sc Radionuclide, 46cSc, 44mSc, 44gSc, 43Sc, and 48V.

The cross-sections of the 48Ti(p,x)47Sc, 46cSc, 44mSc, 44gSc, 43Sc, and 48V nuclear reactions were measured from 18 to 70 MeV, with particular attention to 47Sc production. Enriched 48Ti powder was deposited on an aluminum backing and the obtained targets were characterized via elastic backscattering spectroscopy at the INFN-LNL. Targets were exposed to low-intensity proton irradiation using the stacked-foils technique at the ARRONAX facility. Activated samples were measured using γ-spectrometry; the results were compared with the data int he literature and the theoretical TALYS-based values. A regular trend in the new values obtained from the different irradiation runs was noted, as well as a good agreement with the literature data, for all the radionuclides of interest: 47Sc, 46cSc, 44mSc, 44gSc, 43Sc, and 48V. 47Sc production was also discussed, considering yield and radionuclidic purity, for different 47Sc production scenarios.

Excitation functions of proton-induced nuclear reactions on natCaCO3 up to 60 MeV

47Sc could be used in SPECT imaging and is also suitable for targeted therapy of small tumours. Application of 47Sc is quite promising as theranostic with its diagnostic pair 44Sc or 43Sc. Excitation functions for the production of 47Sc and its accompanying impurities through proton bombardment of natural calcium carbonate (natCaCO3) targets were experimentally evaluated and compared with both previous measurements and TALYS predictions. The integral production yields of 47Sc, as well as the main impurities 44m,46,48Sc, were calculated. The consistency of the results with available experimental data was verified for each reaction. The target yield was determined using the measured activity of the produced radionuclides.

47Sc production with proton beams on isotopically enriched 48Ti and 49Ti targets

The theranostic emerging radionuclide 47Sc is under the spotlight of the scientific community due to its medically favorable decay characteristics (t1/2 =3.3492 d, Eγ=159.381 keV, E β−, mean =162.0 keV) for both the diagnostic and treatment procedures. In the framework of the LaRAMED (LAboratory of RAdionuclides for MEDicine) program at INFN-LNL (National Institute of Nuclear Physics-Legnaro National Laboratories), the investigation of the possible 47Sc production routes using a 70 MeV proton beam is one of the goals of the REMIX (Research on Emerging Medical radIonuclides from the X-sections) project, funded by INFN for the years 2021-2023. Since the LARAMED bunkers are currently under completion, experiments are performed in collaboration with the GIP ARRONAX facility (Nantes, France), where a 70 MeV multi-particle cyclotron is operational. In this work, the cross-section measurements using enriched 48,49Ti targets are reported and the results presented in comparison to the previous literature data, when available. The 47Sc excitation functions are analyzed in relation to the contaminants’ ones since the co-produced radionuclides can affect the dose delivered to a patient. 46Sc cross-section curves are mainly taken into account since 46Sc cannot be chemically separated from 47Sc and its half-life (t1/2=83.79 d) is longer than the 47Sc one (t1/2=3.3492 d).

Research on Emerging Medical radionuclides from the X-sections (REMIX): The Accelerator-based Production of 47Sc, 149Tb, 152Tb, 155Tb and 161Tb

The REMIX project is focused on the cyclotron-based production of 47Sc, 149Tb, 152Tb, 155Tb and 161Tb radionuclides, whose decay characteristics make them suitable for medical applications. This work will outline the main results achieved withing the REMIX collaboration, that is organized in the following Work Packages (WP): WP1. Target manufacturing (49Ti, 50Ti and 155Gd2O3) and characterization; WP2. Nuclear cross section (XS) measurements with 49Ti and 50Ti targets for 47Sc production; WP3. Nuclear XS measurements with natDy, 159Tb and natEu targets for xxTb production; WP4. Nuclear XS modeling for 47Sc and 155Tb production; WP5. Dosimetric calculations for 47Sc- and xxTb-labelled radiopharmaceuticals; WP6. 155Tb Thick Target Yield (TTY) measurements; WP7. Apparatus design and realization for irradiation tests with the LARAMED beamline. Since the LARAMED bunkers and ancillary laboratories are currently under completion at the INFN-LNL, the nuclear XS experiments are carried out in collaboration with the GIP ARRONAX facility (Saint-Herblain, France) and the Thick Target Yield (TTY) measurements are performed at the Sacro Cuore Don Calabria hospital (SCDCh, Negrar, Verona, Italy).

Photonuclear production of 47Ca for 47Ca/47Sc generator from natural CaCO3 targets

This work investigated the indirect production of 47Sc from natural Ca targets via 48Ca(γ,n)47Ca→47Sc + β− + ν‾e with incident electron energies of 30, 35, and 40 MeV. The 47Ca production yields were simulated using the PHITS Monte Carlo simulation code and compared to experimental data. The simulated production rates for all three irradiations are in good agreement with experimental data within uncertainties. As a demonstration of the 47Ca/47Sc generator system, one of the irradiated CaCO3 targets was dissolved in nitric acid, and 47Sc was isolated from the target material using commercially available Eichrom DGA resin. The 47Sc was allowed to grow in, and the purification process was repeated with promising 47Sc and Ca recovery yields.

47Sc and 46Sc cross-section measurement for an optimized 47Sc production with an 18 MeV medical PET cyclotron

The availability of novel radionuclides plays a fundamental role in the development of personalized nuclear medicine. In particular, there is growing interest in pairs formed by two radioisotopes of the same element, the so-called true theranostic pairs, such as 61,64Cu/67Cu, 43,44Sc/47Sc and 155Tb/149,161Tb. In this case, the two radionuclides have identical kinetics and chemical reactivity, allowing to predict whether the patient will benefit from a therapeutic treatment on the basis of nuclear imaging data.47Sc [t1/2 = 3.349 d, Eβ−max = 440.9 keV (68.4%); 600.3 keV (31.6%), Eγ = 159.4 keV (68.3%)] is a promising radionuclide for theranostic applications in nuclear medicine. Its physical characteristics make it suitable for radionuclide therapy and allow SPECT imaging during treatment. Moreover, 47Sc is foreseen as the therapeutic partner of the β+-emitters 43Sc and 44Sc, both under study for PET imaging, opening new avenues towards the true theranostics concept. 47Sc can be produced by proton irradiation of an enriched 50Ti oxide target with a medical cyclotron equipped with a solid target station. To optimize the production yield and the radionuclidic purity, an accurate knowledge of the production cross sections is necessary. In this paper, we report on measurements of the production cross section of 47Sc and 46Sc using enriched 50Ti titanium oxide targets, performed at the Bern University Hospital cyclotron laboratory. On the basis of the obtained results, a study of the production yield and purity was performed to assess the optimal irradiation conditions. A production test was also carried out to confirm these findings.

High purity 47Sc production using high-energy photons and natural vanadium targets

Scandium-47 (47Sc) is of high value for targeted radiotherapy and theranostics; we report a novel, cost-effective approach to produce high-purity 47Sc via photonuclear reactions with natural vanadium. Irradiation at 20 MeV photon end-point energy produces >99.998% pure 47Sc, while irradiation at 38 MeV produces 98.8 ± 1.6% pure 47Sc. Experimental data suggest producing greater than 100 mCi (3700 MBq) of 47Sc using this approach may be feasible. Future research into refinement and scale-up to support pre-clinical research is recommended.

Correction to: Production of 47Sc with natural vanadium targets: results of the PASTA project

Correction to: Production of 47Sc with natural vanadium targets: results of the PASTA project

Theoretical and experimental investigations of Sc-47 production at Egyptian Second Research Reactor (ETRR-2)

The present work was planned to evaluate the reactor production of 47Sc from calcium and titanium targets at Egyptian Second Research Reactor (ETRR-2) based on 46Ca (n, γ) 47Ca $$\mathop{\longrightarrow}\limits^{\beta - }$$ 47Sc and 47Ti (n, p) 47Sc nuclear ractions, respectively. A comparison between the two routs in terms of specific activity of 47Sc and co-produced radioimpurities was carried out. The MCNPX2.7.0 code was used to estimate the levels of all radionuclides produced throughout as well as after the irradiation of 46CaCO3, natTiO2 and 47TiO2 targets. The computational results were verified by experimental measurements, and a good aggrement was found between both. Additionally, our results showed that 47Sc production is greatly preferred from titanium route rather than calcium route.

Calculated cyclotron-based scandium-47 production yields via 48Ca(p, 2n)47Sc nuclear reaction

Scandium-47 is a promising particle emitter that has been suggested as a candidate for radiotheranostics. Thus, better understanding of optimum irradiation parameters, radioactivity yields and possible impurities during its production is of paramount importance. The theoretical calculation of the end-of-bombardment (EOB) results is performed using Microsoft Excel following the calculation of the excitation function obtained from the TALYS software and the stopping power obtained from the SRIM software can be accessed for free. According to the TALYS code calculations, the threshold energy for 47Sc production was 8.39 MeV, whereas the maximum cross-section (879 mbarn) occurred at proton incident energy of 17 MeV. The calculated EOB yield for 48Ca(p,2n)47Sc nuclear reaction at 60 MeV proton energy was found to be 449 MBq/μAh, which was suitable quality for typical radionuclide production. Besides, three radionuclides, i.e. 48Sc, 46Sc and 47Ca were predicted to be the main impurities in the 47Sc production. However, in order to minimize the production of 48Sc, 46Sc and 47Ca impurities radionuclide the safest and optimum proton energy should be between 23 and 30 MeV, which can be achieved using the available 26 MeV cyclotron. This study can be used as a reference for future 47Sc production when proton beams of up to 60 MeV are employed.

AN ESTIMATE OF 47Sc PHOTONUCLEAR YIELD IN A PRODUCTION TARGET

47Sc is considered as a promising beta-emitter for cancer immunotherapy. For its carrier-free production, the 48Ti(γ,p)47Sc reaction in the field of bremsstrahlung radiation of an electron accelerator can be used. On the basis of developed analytical model and a double-foil activation technique, the main characteristics of the photonuclear isotope production and optimal dimensions of a production target have been established. The measured photonuclear yield of 47Sc and dominant scandium admixtures in thin foils of natural titanium in the electron energy range of 35 to 95 MeV enabled to specify the available data on the cross-section of the48Ti(γ,p)47Sc reaction. Using those results, the gross and specific activity of 47Sc in the cylindrical titanium targets of optimal size were calculated by a simulation technique. The comparison of capacity of the photonuclear method of the 47Sc production with other techniques is carried out.

Production of 47Sc with natural vanadium targets: results of the PASTA project

The goal of PASTA project (acronym for production with accelerator of 47Sc for theranostic applications) is the determination of excitation functions associated to several nuclear reactions, aimed at yielding the theranostic radionuclide 47Sc. This work reports the main results obtained by irradiating natural vanadium targets with proton beams up to 70 MeV. Particular care is also given to the co-production of 46Sc, the only isotopic contaminant with half-life longer than 47Sc. Experimental results are compared with theoretical studies by means of known nuclear reaction software tools that are publicly available.

Investigations of proton and deuteron induced nuclear reactions on natural and enriched Titanium, Calcium and Vanadium targets, with special reference to the production of 47Sc

47Sc could be used in SPECT imaging and also suitable for targeted therapy of small tumors. The excitation functions for the production of 47Sc and accompanying impurities via proton and deuteron bombardment of Calcium, Titanium and Vanadium targets were evaluated by three nuclear codes, ALICE, TALYS and EMPIRE. Therefrom, integral yields of 47Sc and also 46gSc as a main impurity were calculated. The various production routes of 47Sc were compared together. The results consistency with available experimental data was checked for each reaction. Based on the results, the 46Ca(d,n)47Sc reaction can leads to the high purity 47Sc with the moderate yield.

PP#87 - 47Sc targetry: investigating the production of 47Sc from 48Ti toward use in targeted radiotherapy

PP#87 - 47Sc targetry: investigating the production of 47Sc from 48Ti toward use in targeted radiotherapy

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.

Cross-section measurement of 44mSc,47Sc, 48Sc and 47Ca for an optimized 47Sc production with an 18 MeV medical PET cyclotron

Novel medical radioisotopes for both diagnostic and therapy are essential for the future development of personalized nuclear medicine. Among them, radiometals can be used to label both proteins and peptides and encompass promising theranostic pairs. The optimized supply of radiometals in quantity and quality for clinical applications represents a scientific and technological challenge.47Sc is a β− emitter that forms a theranostic pair together with one of the β+ emitters 43Sc or 44Sc. It can be produced at a medical cyclotron by proton bombardment of an enriched calcium oxide target. The parasite production of 48Sc undermines the 47Sc purity, which strongly depends on the energy of protons impinging the target and on the thickness of the target material. For this purpose, an accurate knowledge of the production cross-sections is mandatory.In this paper, we report on the measurement of the cross-section of the reactions 44Ca(p,n)44 mSc,48Ca(p,n)48Sc, 48Ca(p,2n)47Sc and 48Ca(p,pn)47Ca using natCaCO3 targets performed at the Bern University Hospital cyclotron laboratory. On the basis of the obtained results and of the isotopic composition of commercially available enriched target materials, the thick target yields and the purity were calculated to assess the optimal irradiation conditions.

47Sc production development by cyclotron irradiation of 48Ca

The therapeutic radionuclide 47Sc was produced through the 48Ca(p,2n) channel on a proton beam accelerator. The obtained results show that the optimum proton energies are in the range of 24–17 MeV, giving the possibility to produce 47Sc radionuclide containing 7.4% of 48Sc. After activation, the powdery CaCO3 target material was dissolved in HCl and scandium isotopes were isolated from the targets. The performed separation experiments indicate that, due to the simplicity of the operations and the chemical purity of the obtained 47Sc the best separation process is when scandium radioisotopes are separated on the 0.2 µm filter.