Evaluation of the cyclotron production of 165Er by different reactions

Zandi, Nadia; Sadeghi, Mahdi; Afarideh, H.

doi:10.1007/s10967-012-2116-0

Cited by 12 publications

(8 citation statements)

References 18 publications

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“…At the cyclotron of Orléans, two ways of production have been explored. All cross sections were known and obtained by irradiation or simulation from calculation codes (ALICE-IPPE) [12,13,26,27].…”

Section: Methods For 165 Er (An Emitter Auger Electron and Bimodality)mentioning

confidence: 99%

First Steps at the Cyclotron of Orléans in the Radiochemistry of Radiometals: 52Mn and 165Er

et al. 2018

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This work describes the first real developments in radiochemistry around exotic radionuclides at the cyclotron of Orléans focusing on the radiochemistry of two radiometals 165 Er and 52 Mn. For these developments, targets were irradiated during 0.5-2 h at a maximum current of 2 µA. All activities have been determined by radiotracer method. The production of 165 Er from a natural Ho target that was irradiated is described. Higher activities of 165 Er were obtained via deuteron irradiation then proton with lower ratio 165 Er/ 166 Ho (400/1 to 8/1). By using LN2 resin, the separation of adjacent lanthanides was made on various concentrations of HNO 3 (0.3 to 5 M). Weight coefficients (Dw) were defined in a batch test. Then, the first tests of separation on a semi-automated system were made: the ratio 166+nat Ho/ 165 Er in an isolated fraction was significantly reduced (1294 ± 1183 (n = 3)) but the reliability and reproducibility of the system must be improved. Then, a new Cr powder-based target for 52 Mn production was designed. Its physical aspects such as mechanics, thermal resistance and porosity have been studied. Dw for various compositions of eluent Ethanol/HCl were evaluated by reducing contact time (1 h) comparative to the literature. A first evaluation of semi-automated separation Cr/Mn has been made.Instruments 2018, 2, 15 2 of 23 cyclotron of Orléans is of interest in producing radionuclides for analytical applications allowing for the validation of the separation by the radiotracer method [9] and a method as sensitive as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In this context, it was necessary to initiate tools and methodology in radiochemistry to develop further the accelerator in the area of medical radionuclides. However, two constraints relative to the choice of radionuclides were met at the cyclotron of Orléans. The first constraint was to produce gamma emission and the second was that the half-life of the radionuclide produced must be below 100 days (due to nuclear waste management considerations). Hence for the following work, we used 165 Er/Er, 166 Ho/Ho, 51 Cr/Cr and 52 Mn/Mn. Other tools to improve radiochemical separation based on resins, methodology, and target design must be developed. Two cases hereafter illustrate the method's development for the production and subsequent separation of 165 Er and 52 Mn.Instruments 2018, 3, 15 2 of 22 radionuclides for analytical applications allowing for the validation of the separation by the radiotracer method [9] and a method as sensitive as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In this context, it was necessary to initiate tools and methodology in radiochemistry to develop further the accelerator in the area of medical radionuclides. However, two constraints relative to the choice of radionuclides were met at the cyclotron of Orléans. The first constraint was to produce gamma emission and the second was that the half-life of the radionuclide produced must be below 100 days (due to nuclear waste management considerations)...

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Section: Methods For 165 Er (An Emitter Auger Electron and Bimodality)mentioning

confidence: 99%

First Steps at the Cyclotron of Orléans in the Radiochemistry of Radiometals: 52Mn and 165Er

et al. 2018

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“…There have been a number of nuclear reaction routes reported for the production of 165 Er, typically using protons, deuterons or neutrons as the bombardment particles with either natural or enriched Er targets, or natural Ho targets (100% natural abundance of 165 Ho) (Sadeghi et al 2010 ; Zandi et al 2013 ; Beyer et al 2004b ; Tárkányi et al 2007 , 2008a , b , c , 2009 ; Hermanne et al 2013 ). The use of natural Er targets utilises the generator approach to produce ingrown 165 Er after the β − -decay of 165 Tm produced via either the nat Er(p,xn) 165 Tm → 165 Er or the nat Er(d,xn) 165 Tm → 165 Er nuclear reactions, giving the resultant 165 Er in no-carrier-added form after separation from the target material (Tárkányi et al 2007 ; Vaudon et al 2018 ).…”

Section: Erbium: 169 Er ...mentioning

confidence: 99%

“…Enriched 166 Er targets for the 166 Er(p,2n) 165 Er nuclear reaction are expensive and have therefore led to shifts in research focus to 165 Ho targets paired with proton and deuteron bombardment, with subsequent chemical separation (Tárkányi et al 2008b , c ). These production methods have been favoured due to the fact that they exhibit lower target material costs due to the 100% natural abundance of 165 Ho, and the feasibility of the 165 Ho(p,n) 165 Er and 165 Ho(d,2n) 165 Er nuclear reactions which can be achieved at commercial cyclotrons already in operation using proton and deuteron beams of lower energies (< 20 MeV) (Zandi et al 2013 ; Tárkányi et al 2008b , c ; Vaudon et al 2018 ). Of these two nuclear reactions, the deuteron reaction has been reported to produce larger amounts of 165 Er activity at low-energy cyclotrons, but with the trade-off of higher amounts of 166 Ho as an impurity, with 165 Er/ 166 Ho ratios of ~ 400/1 c.f.…”

Section: Erbium: 169 Er ...mentioning

confidence: 99%

“…Despite the previous intimation that enriched 166 Er targets are prohibitively expensive, work has progressed on evaluating the feasibility of both the 166 Er(p,2n) 165 Tm → 165 Er and the 166 Er(d,3n) 165 Tm → 165 Er cyclotron production methods (Sadeghi et al 2010 ; Zandi et al 2013 ). Calculations have been performed using the ALICE/ASH and EMPIRE-3.1 codes for nuclear reactions to evaluate the excitation functions, yields and target thicknesses that are optimum for the four routes to 165 Er, namely 166 Er(p,2n) 165 Tm → 165 Er, nat Er(p,x) 165 Tm → 165 Er, 165 Ho(p,n) 165 Er and 165 Ho(d,2n) 165 Er, and these have been compared against experimental data obtained from other investigations (Zandi et al 2013 ). From these data, it was concluded that the proton irradiation of 166 Er for the generator production of 165 Er from 165 Tm afforded the highest production yield of 165 Er in no-carrier-added form (Zandi et al 2013 ).…”

Section: Erbium: 169 Er ...mentioning

confidence: 99%

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Cutting edge rare earth radiometals: prospects for cancer theranostics

Sadler

Hogan

Fraser

et al. 2022

EJNMMI radiopharm. chem.

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Background With recent advances in novel approaches to cancer therapy and imaging, the application of theranostic techniques in personalised medicine has emerged as a very promising avenue of research inquiry in recent years. Interest has been directed towards the theranostic potential of Rare Earth radiometals due to their closely related chemical properties which allow for their facile and interchangeable incorporation into identical bifunctional chelators or targeting biomolecules for use in a diverse range of cancer imaging and therapeutic applications without additional modification, i.e. a “one-size-fits-all” approach. This review will focus on recent progress and innovations in the area of Rare Earth radionuclides for theranostic applications by providing a detailed snapshot of their current state of production by means of nuclear reactions, subsequent promising theranostic capabilities in the clinic, as well as a discussion of factors that have impacted upon their progress through the theranostic drug development pipeline. Main body In light of this interest, a great deal of research has also been focussed towards certain under-utilised Rare Earth radionuclides with diverse and favourable decay characteristics which span the broad spectrum of most cancer imaging and therapeutic applications, with potential nuclides suitable for α-therapy (149Tb), β−-therapy (47Sc, 161Tb, 166Ho, 153Sm, 169Er, 149Pm, 143Pr, 170Tm), Auger electron (AE) therapy (161Tb, 135La, 165Er), positron emission tomography (43Sc, 44Sc, 149Tb, 152Tb, 132La, 133La), and single photon emission computed tomography (47Sc, 155Tb, 152Tb, 161Tb, 166Ho, 153Sm, 149Pm, 170Tm). For a number of the aforementioned radionuclides, their progression from ‘bench to bedside’ has been hamstrung by lack of availability due to production and purification methods requiring further optimisation. Conclusions In order to exploit the potential of these radionuclides, reliable and economical production and purification methods that provide the desired radionuclides in high yield and purity are required. With more reactors around the world being decommissioned in future, solutions to radionuclide production issues will likely be found in a greater focus on linear accelerator and cyclotron infrastructure and production methods, as well as mass separation methods. Recent progress towards the optimisation of these and other radionuclide production and purification methods has increased the feasibility of utilising Rare Earth radiometals in both preclinical and clinical settings, thereby placing them at the forefront of radiometals research for cancer theranostics.

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“…However, for the treatment of micrometastatic or disseminated cancers, radiopharmaceuticals emitting shorter range, higher linear energy Proton, deuteron, or alpha particle irradiation of erbium or holmium targets produces no-carrier-added 165 Er through a variety of nuclear reaction routes [14]. Proton or deuteron irradiation of erbium produces 165 Tm (t 1/2 = 30.06 h) via nat Er(p,xn) 165 Tm [15,16] or nat Er(d,xn) 165 Tm [17], respectively, which can be chemically isolated prior to its β − decay to 165 Er. While these routes offer high 165 Er yields, they require a medium energy, multiparticle research cyclotron and expensive, isotopically enriched targets for highest yields.…”

Section: Introductionmentioning

confidence: 99%

A High Separation Factor for 165Er from Ho for Targeted Radionuclide Therapy

et al. 2021

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Background: Radionuclides emitting Auger electrons (AEs) with low (0.02–50 keV) energy, short (0.0007–40 µm) range, and high (1–10 keV/µm) linear energy transfer may have an important role in the targeted radionuclide therapy of metastatic and disseminated disease. Erbium-165 is a pure AE-emitting radionuclide that is chemically matched to clinical therapeutic radionuclide 177Lu, making it a useful tool for fundamental studies on the biological effects of AEs. This work develops new biomedical cyclotron irradiation and radiochemical isolation methods to produce 165Er suitable for targeted radionuclide therapeutic studies and characterizes a new such agent targeting prostate-specific membrane antigen. Methods: Biomedical cyclotrons proton-irradiated spot-welded Ho(m) targets to produce 165Er, which was isolated via cation exchange chromatography (AG 50W-X8, 200–400 mesh, 20 mL) using alpha-hydroxyisobutyrate (70 mM, pH 4.7) followed by LN2 (20–50 µm, 1.3 mL) and bDGA (50–100 µm, 0.2 mL) extraction chromatography. The purified 165Er was radiolabeled with standard radiometal chelators and used to produce and characterize a new AE-emitting radiopharmaceutical, [165Er]PSMA-617. Results: Irradiation of 80–180 mg natHo targets with 40 µA of 11–12.5 MeV protons produced 165Er at 20–30 MBq·µA−1·h−1. The 4.9 ± 0.7 h radiochemical isolation yielded 165Er in 0.01 M HCl (400 µL) with decay-corrected (DC) yield of 64 ± 2% and a Ho/165Er separation factor of (2.8 ± 1.1) · 105. Radiolabeling experiments synthesized [165Er]PSMA-617 at DC molar activities of 37–130 GBq·µmol−1. Conclusions: A 2 h biomedical cyclotron irradiation and 5 h radiochemical separation produced GBq-scale 165Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutics. This will enable fundamental radiation biology experiments of pure AE-emitting therapeutic radiopharmaceuticals such as [165Er]PSMA-617, which will be used to understand the impact of AEs in PSMA-targeted radionuclide therapy of prostate cancer.

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Evaluation of the cyclotron production of 165Er by different reactions

Cited by 12 publications

References 18 publications

First Steps at the Cyclotron of Orléans in the Radiochemistry of Radiometals: 52Mn and 165Er

First Steps at the Cyclotron of Orléans in the Radiochemistry of Radiometals: 52Mn and 165Er

Cutting edge rare earth radiometals: prospects for cancer theranostics

A High Separation Factor for 165Er from Ho for Targeted Radionuclide Therapy

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