The Metamorphosis of Radionuclide Production and Development at Paul Scherrer Institute

Grundler, Pascal V.; Eichler, Robert; Talip, Zeynep; Schubiger, P. A.; Schibli, Roger; Meulen, Nicholas P. van der

doi:10.2533/chimia.2020.968

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…A 50- μ A current is peeled off from the main beam of 2.5 mA delivered by Injector II. Behind the beam splitter, the proton beam is directed towards an irradiation station named IP2 ( van der Meulen et al, 2020a ; Grundler et al, 2020 ). The proton beam energy is degraded by means of cooling water and niobium foils.…”

Section: Methodsmentioning

confidence: 99%

Study of thulium-167 cyclotron production: a potential medically-relevant radionuclide

Renaldin,

Dellepiane,

Braccini

et al. 2023

Front. Chem.

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Introduction: Targeted Radionuclide Therapy is used for the treatment of tumors in nuclear medicine, while sparing healthy tissues. Its application to cancer treatment is expanding. In particular, Auger-electron emitters potentially exhibit high efficacy in treating either small metastases or single tumor cells due to their short range in tissue. The aim of this paper is to study the feasibility of a large-scale production of thulium-167, an Auger-electron emitter radionuclide, in view of eventual systematic preclinical studies.Methods: Proton-irradiated enriched erbium-167 and erbium-168 oxides were used to measure the production cross sections of thulium-165, thulium-166, thulium-167, and thulium-168 utilizing an 18-MeV medical cyclotron equipped with a Beam Transport Line (BTL) at the Bern medical cyclotron laboratory. The comparison between the experimental and the TENDL 2021 theoretical cross-section results were in good agreement. Additional experiments were performed to assess the production yields of thulium radioisotopes in the BTL. Thulium-167 production yield was also measured irradiating five different target materials (167Er2O3, 168Er2O3, natTm2O3, natYb2O3, 171Yb2O3) with proton beams up to 63 MeV at the Injector II cyclotron of Paul Scherrer Institute.Results and Discussion: Our experiments showed that an 8-h irradiation of enriched ytterbium-171 oxide produced about 420 MBq of thulium-167 with a radionuclidic purity of 99.95% after 5 days of cooling time with a proton beam of about 53 MeV. Larger activities of thulium-167 can be achieved using enriched erbium-168 oxide with a 23-MeV proton beam, obtaining about 1 GBq after 8-h irradiation with a radionuclidic purity of <99.5% 5 days post end of bombardment.

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Section: Methodsmentioning

confidence: 99%

Study of thulium-167 cyclotron production: a potential medically-relevant radionuclide

Renaldin,

Dellepiane,

Braccini

et al. 2023

Front. Chem.

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“…The pellets produced by compression of the enriched material were encapsulated in aluminum (99.5% pure) capsules specifically designed in-house for PSI’s IP2 irradiation station (Grundler et al 2020 ; van der Meulen et al 2020a ) (Fig. 2 ).…”

Section: Methodsmentioning

confidence: 99%

“…The beam current was set to 50 µA. Niobium discs (3.4 mm and 2.4 mm, respectively) were used as degraders to decrease the proton energy from 72 MeV to the desired energy windows (Grundler et al 2020 ; van der Meulen et al 2015 , 2020a ). The thicknesses of the degraders were calculated using SRIM-2013 (Ziegler et al 2010 ).…”

Section: Methodsmentioning

confidence: 99%

Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging

Favaretto

Talip

Borgna

et al. 2021

EJNMMI radiopharm. chem.

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Background Terbium-155 [T1/2 = 5.32 d, Eγ = 87 keV (32%) 105 keV (25%)] is an interesting radionuclide suitable for single photon emission computed tomography (SPECT) imaging with potential application in the diagnosis of oncological disease. It shows similar decay characteristics to the clinically established indium-111 and would be a useful substitute for the diagnosis and prospective dosimetry with biomolecules that are afterwards labeled with therapeutic radiolanthanides and pseudo-radiolanthanides, such as lutetium-177 and yttrium-90. Moreover, terbium-155 could form part of the perfect “matched pair” with the therapeutic radionuclide terbium-161, making the concept of true radiotheragnostics a reality. The aim of this study was the investigation of the production of terbium-155 via the 155Gd(p,n)155Tb and 156Gd(p,2n)155Tb nuclear reactions and its subsequent purification, in order to obtain a final product in quantity and quality sufficient for preclinical application. The 156Gd(p,2n)155Tb nuclear reaction was performed with 72 MeV protons (degraded to ~ 23 MeV), while the 155Gd(p,n)155Tb reaction was degraded further to ~ 10 MeV, as well as performed at an 18 MeV medical cyclotron, to demonstrate its feasibility of production. Result The 156Gd(p,2n)155Tb nuclear reaction demonstrated higher production yields of up to 1.7 GBq, however, lower radionuclidic purity when compared to the final product (~ 200 MBq) of the 155Gd(p,n)155Tb nuclear reaction. In particular, other radioisotopes of terbium were produced as side products. The radiochemical purification of terbium-155 from the target material was developed to provide up to 1.0 GBq product in a small volume (~ 1 mL 0.05 M HCl), suitable for radiolabeling purposes. The high chemical purity of terbium-155 was proven by radiolabeling experiments at molar activities up to 100 MBq/nmol. SPECT/CT experiments were performed in tumor-bearing mice using [155Tb]Tb-DOTATOC. Conclusion This study demonstrated two possible production routes for high activities of terbium-155 using a cyclotron, indicating that the radionuclide is more accessible than the exclusive mass-separated method previously demonstrated. The developed radiochemical purification of terbium-155 from the target material yielded [155Tb]TbCl3 in high chemical purity. As a result, initial cell uptake investigations, as well as SPECT/CT in vivo studies with [155Tb]Tb-DOTATOC, were successfully performed, indicating that the chemical separation produced a product with suitable quality for preclinical studies.

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“…nat Er 2 O 3 target discs, 6 mm in diameter, were prepared and irradiated at the PSI's IP2 irradiation station ( 30 ), using the 72 MeV proton beam from Injector II separated sector cyclotron. Experimental cross-section results of nat Er 2 O 3 were previously reported by Tarkanyi et al ( 31 ).…”

Section: Experimental Setup and Methodsmentioning

confidence: 99%

Efficient Production of High Specific Activity Thulium-167 at Paul Scherrer Institute and CERN-MEDICIS

et al. 2021

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Thulium-167 is a promising radionuclide for nuclear medicine applications with potential use for both diagnosis and therapy (“theragnostics”) in disseminated tumor cells and small metastases, due to suitable gamma-line as well as conversion/Auger electron energies. However, adequate delivery methods are yet to be developed and accompanying radiobiological effects to be investigated, demanding the availability of 167Tm in appropriate activities and quality. We report herein on the production of radionuclidically pure 167Tm from proton-irradiated natural erbium oxide targets at a cyclotron and subsequent ion beam mass separation at the CERN-MEDICIS facility, with a particular focus on the process efficiency. Development of the mass separation process with studies on stable 169Tm yielded 65 and 60% for pure and erbium-excess samples. An enhancement factor of thulium ion beam over that of erbium of up to several 104 was shown by utilizing laser resonance ionization and exploiting differences in their vapor pressures. Three 167Tm samples produced at the IP2 irradiation station, receiving 22.8 MeV protons from Injector II at Paul Scherrer Institute (PSI), were mass separated with collected radionuclide efficiencies between 11 and 20%. Ion beam sputtering from the collection foils was identified as a limiting factor. In-situ gamma-measurements showed that up to 45% separation efficiency could be fully collected if these limits are overcome. Comparative analyses show possible neighboring mass suppression factors of more than 1,000, and overall 167Tm/Er purity increase in the same range. Both the actual achieved collection and separation efficiencies present the highest values for the mass separation of external radionuclide sources at MEDICIS to date.

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The Metamorphosis of Radionuclide Production and Development at Paul Scherrer Institute

Cited by 8 publications

References 37 publications

Study of thulium-167 cyclotron production: a potential medically-relevant radionuclide

Study of thulium-167 cyclotron production: a potential medically-relevant radionuclide

Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging

Efficient Production of High Specific Activity Thulium-167 at Paul Scherrer Institute and CERN-MEDICIS

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