Development of radionuclides for innovative radiopharmaceuticals

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An important component of innovative radiopharmaceuticals, especially in oncology is the availability of alternative radionuclides with optimal decay properties, which allow to improve diagnostic or therapeutic efficiency. Currently a variety of accelerator, reactor (or Spallation Neutron Source) and generator produced radionuclides are developed and produced at PSI. Medical radionuclide must be available with high specific activity and purity. Here the choice of the nuclear reaction and subsequent radiochemical isolation strategy play a key role.

Localization and tracking of radio pharmaceuticals in vivo is performed by single photon emission computed tomography (SPECT) as well as by positron emission tomography (PET). The therapeutic radionuclides are particle emitters that are able to deposit a high quantity of energy in small volumes via a high "linear energy transfer" (LET). Here β-, α and also Auger electron emitters are used or considered to be useful for the therapeutic treatment.

The research group Radionuclide Development is a joint research group of the Laboratory of Radiochemistry and of the Center of Radiopharmaceutical Sciences at PSI. 

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    Unraveling the formation of Tb/Pd films by coupled reduction as targets for heavy ion-beam irradiation
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    First-in-human administration of [161Tb]Tb-SibuDAB and comparative dosimetry with standard [177Lu]Lu-PSMA-I&T as part of the PROGNOSTICS phase Ia study
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    DORA PSI
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    DORA PSI
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    Preclinical comparison of (radio)lanthanides using mass spectrometry and nuclear imaging techniques: biodistribution of lanthanide-based tumor-targeting agents and lanthanides in ionic form
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    DORA PSI
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    DORA PSI
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    DORA PSI
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    DORA PSI
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    First-in-human administration of terbium-161-labelled somatostatin receptor subtype 2 antagonist ([161Tb]Tb-DOTA-LM3) in a patient with a metastatic neuroendocrine tumour of the ileum
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    DORA PSI
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    Comparison of the dosimetry of scandium-43 and scandium-44 patient organ doses in relation to commonly used gallium-68 for imaging neuroendocrine tumours
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    DORA PSI
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    Preclinical evaluation of gastrin-releasing peptide receptor antagonists labeled with 161Tb and 177Lu: a comparative study
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    DORA PSI
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    Terbium sisters: current development status and upscaling opportunities
    Frontiers in Nuclear Medicine. 2024; 4: 1472500 (14 pp.). https://doi.org/10.3389/fnume.2024.1472500
    DORA PSI
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    Terbium "Sisters": more than just a "Swiss Army Knife"
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    DORA PSI
  • Pautz A, Eichler R, van der Meulen NP
    Development of radionuclides for theragnostic applications at the Paul Scherrer Institut (PSI)
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    EJNMMI Radiopharmacy and Chemistry. 2024; 9: 42 (20 pp.). https://doi.org/10.1186/s41181-024-00268-w
    DORA PSI
  • Beyer D, Vaccarin C, Deupi X, Mapanao AK, Cohrs S, Sozzi-Guo F, et al.
    A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides
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    DORA PSI
  • Dellepiane G, Casolaro P, Favaretto C, Gottstein A, Grundler PV, Mateu I, et al.
    Cross-section measurement of thulium radioisotopes with an 18 MeV medical PET cyclotron for an optimized 165Er production
    Applied Radiation and Isotopes. 2023; 200: 110954 (11 pp.). https://doi.org/10.1016/j.apradiso.2023.110954
    DORA PSI
  • Favaretto C, Grundler PV, Talip Z, Landolt S, Sepini L, Köster U, et al.
    161Tb-DOTATOC production using a fully automated disposable cassette system: a first step toward the introduction of 161Tb into the clinic
    Journal of Nuclear Medicine. 2023; 64(7): 1138-1144. https://doi.org/10.2967/jnumed.122.265268
    DORA PSI
  • Happl B, Brandt M, Balber T, Benčurová K, Talip Z, Voegele A, et al.
    Synthesis and preclinical evaluation of radiolabeled [103Ru]BOLD-100
    Pharmaceutics. 2023; 15(11): 2626 (11 pp.). https://doi.org/10.3390/pharmaceutics15112626
    DORA PSI
  • Juget F, Durán T, Nedjadi Y, Talip Z, Grundler PV, Favaretto C, et al.
    Activity measurement of 44Sc and calibration of activity measurement instruments on production sites and clinics
    Molecules. 2023; 28(3): 1345 (10 pp.). https://doi.org/10.3390/molecules28031345
    DORA PSI
  • Müller C, van der Meulen NP, Schibli R
    Opportunities and potential challenges of using terbium-161 for targeted radionuclide therapy in clinics
    European Journal of Nuclear Medicine and Molecular Imaging. 2023; 50: 3181-3184. https://doi.org/10.1007/s00259-023-06316-y
    DORA PSI
  • Renaldin E, Dellepiane G, Braccini S, Sommerhalder A, Zhang H, van der Meulen NP, et al.
    Study of thulium-167 cyclotron production: a potential medically-relevant radionuclide
    Frontiers in Chemistry. 2023; 11: 1288588 (14 pp.). https://doi.org/10.3389/fchem.2023.1288588
    DORA PSI
  • Tschan VJ, Busslinger SD, Bernhardt P, Grundler PV, Zeevaart JR, Köster U, et al.
    Albumin-binding and conventional PSMA ligands in combination with 161Tb: biodistribution, dosimetry, and preclinical therapy
    Journal of Nuclear Medicine. 2023; 64(10): 1625-1631. https://doi.org/10.2967/jnumed.123.265524
    DORA PSI
  • Borgna F, Haller S, Monné Rodriguez JM, Ginj M, Grundler PV, Zeevaart JR, et al.
    Combination of terbium-161 with somatostatin receptor antagonists - a potential paradigm shift for the treatment of neuroendocrine neoplasms
    European Journal of Nuclear Medicine and Molecular Imaging. 2022; 49: 1113-1126. https://doi.org/10.1007/s00259-021-05564-0
    DORA PSI
  • Braccini S, Carzaniga TS, Dellepiane G, Grundler PV, Scampoli P, van der Meulen NP, et al.
    Optimization of 68Ga production at an 18 MeV medical cyclotron with solid targets by means of cross-section measurement of 66Ga, 67Ga and 68Ga
    Applied Radiation and Isotopes. 2022; 186: 110252 (9 pp.). https://doi.org/10.1016/j.apradiso.2022.110252
    DORA PSI
  • Dellepiane G, Casolaro P, Favaretto C, Grundler PV, Mateu I, Scampoli P, et al.
    Cross section measurement of terbium radioisotopes for an optimized 155Tb production with an 18 MeV medical PET cyclotron
    Applied Radiation and Isotopes. 2022; 184: 110175 (14 pp.). https://doi.org/10.1016/j.apradiso.2022.110175
    DORA PSI
  • Durán MT, Juget F, Nedjadi Y, Bailat C, Grundler PV, Talip Z, et al.
    Half-life measurement of 44Sc and 44mSc
    Applied Radiation and Isotopes. 2022; 190: 110507 (10 pp.). https://doi.org/10.1016/j.apradiso.2022.110507
    DORA PSI
  • Eichler R, Kiselev D, Koschik A, Knecht A, van der Meulen N, Scheibl R, et al.
    IMPACT conceptual design report
    Villigen PSI: Paul Scherrer Institut; 2022. PSI Bericht: 22-01.
    DORA PSI
  • Hemmingsson J, Svensson J, van der Meulen NP, Müller C, Bernhardt P
    Active bone marrow S-values for the low-energy electron emitter terbium-161 compared to S-values for lutetium-177 and yttrium-90
    EJNMMI Physics. 2022; 9(1): 65 (13 pp.). https://doi.org/10.1186/s40658-022-00495-7
    DORA PSI
  • Juget F, Talip Z, Nedjadi Y, Durán MT, Grundler PV, Zeevaart JR, et al.
    Precise activity measurements of medical radionuclides using an ionization chamber: a case study with Terbium-161
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    DORA PSI
  • Tosato M, Verona M, Favaretto C, Pometti M, Zanoni G, Scopelliti F, et al.
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    Highlight selection of radiochemistry and radiopharmacy developments by editorial board
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    DORA PSI
  • Baum RP, Singh A, Kulkarni HR, Bernhardt P, Rydén T, Schuchardt C, et al.
    First-in-human application of terbium-161: a feasibility study using 161Tb-DOTATOC
    Journal of Nuclear Medicine. 2021; 62(10): 1391-1397. https://doi.org/10.2967/jnumed.120.258376
    DORA PSI
  • Bernhardt P, Svensson J, Hemmingsson J, van der Meulen NP, Zeevaart JR, Konijnenberg MW, et al.
    Dosimetric analysis of the short-ranged particle emitter 161Tb for radionuclide therapy of metastatic prostate cancer
    Cancers. 2021; 13(9): 2011 (13 pp.). https://doi.org/10.3390/cancers13092011
    DORA PSI
  • Borgna F, Barritt P, Grundler PV, Talip Z, Cohrs S, Zeevaart JR, et al.
    Simultaneous visualization of 161Tb-and 177Lu-labeled somatostatin analogues using dual-isotope SPECT imaging
    Pharmaceutics. 2021; 13(4): 536 (13 pp.). https://doi.org/10.3390/pharmaceutics13040536
    DORA PSI
  • Duchemin C, Ramos JP, Stora T, Ahmed E, Aubert E, Audouin N, et al.
    CERN-MEDICIS: a review since commissioning in 2017
    Frontiers in Medicine. 2021; 8: 693682 (11 pp.). https://doi.org/10.3389/fmed.2021.693682
    DORA PSI
  • Durán MT, Juget F, Nedjadi Y, Bochud F, Talip Z, van der Meulen NP, et al.
    Ytterbium-175 half-life determination
    Applied Radiation and Isotopes. 2021; 176: 109893 (8 pp.). https://doi.org/10.1016/j.apradiso.2021.109893
    DORA PSI
  • Favaretto C, Talip Z, Borgna F, Grundler PV, Dellepiane G, Sommerhalder A, et al.
    Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
    EJNMMI Radiopharmacy and Chemistry. 2021; 6: 37 (17 pp.). https://doi.org/10.1186/s41181-021-00153-w
    DORA PSI
  • Heinke R, Chevallay E, Chrysalidis K, Cocolios TE, Duchemin C, Fedosseev VN, et al.
    Efficient production of high specific activity thulium-167 at Paul Scherrer Institute and CERN-MEDICIS
    Frontiers in Medicine. 2021; 8: 712374 (17 pp.). https://doi.org/10.3389/fmed.2021.712374
    DORA PSI
  • Juget F, Talip Z, Buchillier T, Durán MT, Nedjadi Y, Desorgher L, et al.
    Determination of the gamma and X-ray emission intensities of terbium-161
    Applied Radiation and Isotopes. 2021; 174: 109770 (6 pp.). https://doi.org/10.1016/j.apradiso.2021.109770
    DORA PSI
  • Lima TVM, Gnesin S, Strobel K, del Sol Pérez M, Roos JE, Müller C, et al.
    Fifty shades of scandium: comparative study of PET capabilities using Sc-43 and Sc-44 with respect to conventional clinical radionuclides
    Diagnostics. 2021; 11(10): 1826 (11 pp.). https://doi.org/10.3390/diagnostics11101826
    DORA PSI
  • Müller C, Schibli R, Bernhardt P, Köster U, van der Meulen NP
    Terbium radionuclides for theranostics
    In: Caplan MJ, ed. Reference module in biomedical sciences. sine loco: Elsevier; 2021:(12 pp.). https://doi.org/10.1016/B978-0-12-822960-6.00076-4
    DORA PSI
  • Steyn GF, van der Walt TN, Szelecsényi F, Perrang C, Brümmer JW, Vermeulen C, et al.
    Large-scale production of 88Y and 88Zr/88Y generators: a proof of concept study for a 70 MeV H- cyclotron
    Applied Radiation and Isotopes. 2021; 168: 109469 (11 pp.). https://doi.org/10.1016/j.apradiso.2020.109469
    DORA PSI
  • Taddio MF, Castro Jaramillo CA, Runge P, Blanc A, Keller C, Talip Z, et al.
    In vivo imaging of local inflammation: monitoring LPS-induced CD80/CD86 upregulation by PET
    Molecular Imaging and Biology. 2021; 23: 196-207. https://doi.org/10.1007/s11307-020-01543-3
    DORA PSI
  • Talip Z, Juget F, Ulrich J, Nedjadi Y, Buchillier T, Durán MT, et al.
    Determination of the gamma and X-ray emission intensities of erbium-169
    Applied Radiation and Isotopes. 2021; 176: 109823 (9 pp.). https://doi.org/10.1016/j.apradiso.2021.109823
    DORA PSI
  • Talip Z, Borgna F, Müller C, Ulrich J, Duchemin C, Ramos JP, et al.
    Production of mass-separated erbium-169 towards the first preclinical in vitro investigations
    Frontiers in Medicine. 2021; 8: 643175 (11 pp.). https://doi.org/10.3389/fmed.2021.643175
    DORA PSI
  • van der Meulen NP, Strobel K, Lima TVM
    New radionuclides and technological advances in SPECT and PET scanners
    Cancers. 2021; 13(24): 6183 (15 pp.). https://doi.org/10.3390/cancers13246183
    DORA PSI
  • van der Meulen NP, Talip Z
    Non-conventional radionuclides: the pursuit for perfection
    In: Caplan MJ, ed. Reference module in biomedical sciences. sine loco: Elsevier; 2021:(10 pp.). https://doi.org/10.1016/B978-0-12-822960-6.00052-1
    DORA PSI
  • Durán MT, Juget F, Nedjadi Y, Bochud F, Grundler PV, Gracheva N, et al.
    Determination of 161Tb half-life by three measurement methods
    Applied Radiation and Isotopes. 2020; 159: 109085 (9 pp.). https://doi.org/10.1016/j.apradiso.2020.109085
    DORA PSI
  • Gracheva N, Carzaniga TS, Schibli R, Braccini S, van der Meulen NP
    165Er: a new candidate for Auger electron therapy and its possible cyclotron production from natural holmium targets
    Applied Radiation and Isotopes. 2020; 159: 109079 (8 pp.). https://doi.org/10.1016/j.apradiso.2020.109079
    DORA PSI
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