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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    DORA PSI
  • Chirindel A, Nicolas GP, Westerbergh F, McDougall L, Schmid DE, Geistlich S, et al.
    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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    Light-induced synthesis and radiotheranostic treatment of gastric cancer with 161Tb-labeled monoclonal antibodies
    JACS Au. 2025. https://doi.org/10.1021/jacsau.5c00219
    DORA PSI
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    Preclinical investigation of [149Tb]Tb-DOTATATE and [149Tb]Tb-DOTA-LM3 for tumor-targeted alpha therapy
    European Journal of Nuclear Medicine and Molecular Imaging. 2025; 52: 1383-1398. https://doi.org/10.1007/s00259-024-07035-8
    DORA PSI
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    161Tb Radioimmunotherapy as a treatment for CD30-positive lymphomas
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    DORA PSI
  • Todorov TZ, Coelho R, Dellea S, Jacob F, Heinzelmann-Schwarz V, Grundler PV, et al.
    161Tb-based anti-L1CAM radioimmunotherapy shows superior efficacy in eliminating ovarian cancer stem cells compared with 177Lu in preclinical models of ovarian cancer
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    DORA PSI
  • Tosato M, Favaretto C, Kleynhans J, Burgoyne AR, Gestin JF, van der Meulen NP, et al.
    Alpha Atlas: mapping global production of α-emitting radionuclides for targeted alpha therapy
    Nuclear Medicine and Biology. 2025; 142-143: 108990 (23 pp.). https://doi.org/10.1016/j.nucmedbio.2024.108990
    DORA PSI
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    Development of lisinopril radioconjugates for nuclear imaging of the angiotensin converting enzyme
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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
    European Journal of Nuclear Medicine and Molecular Imaging. 2025; 52: 1370-1382. https://doi.org/10.1007/s00259-024-07018-9
    DORA PSI
  • Wilson JM, Herrmann D, Grundler PV, van der Meulen NP, Sommerhalder A, Steinegger P
    Quantitative gas-phase separation of carrier-free thallium radioisotopes from proton-irradiated natHgO
    Journal of Radioanalytical and Nuclear Chemistry. 2025: 111581 (6 pp.). https://doi.org/10.1007/s10967-025-10125-y
    DORA PSI
  • Busslinger SD, Mapanao AK, Kegler K, Bernhardt P, Flühmann F, Fricke J, et al.
    Comparison of the tolerability of 161Tb- and 177Lu-labeled somatostatin analogues in the preclinical setting
    European Journal of Nuclear Medicine and Molecular Imaging. 2024; 51: 4049-4061. https://doi.org/10.1007/s00259-024-06827-2
    DORA PSI
  • Favaretto C, Grundler PV, Talip Z, Köster U, Johnston K, Busslinger SD, et al.
    Terbium-149 production: a focus on yield and quality improvement towards preclinical application
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    DORA PSI
  • Fricke J, Westerbergh F, McDougall L, Favaretto C, Christ E, Nicolas GP, et al.
    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
    European Journal of Nuclear Medicine and Molecular Imaging. 2024; 51: 2517-2519. https://doi.org/10.1007/s00259-024-06641-w
    DORA PSI
  • Gomes CV, Mendes BM, Paixão L, Gnesin S, Müller C, van der Meulen NP, et al.
    Comparison of the dosimetry of scandium-43 and scandium-44 patient organ doses in relation to commonly used gallium-68 for imaging neuroendocrine tumours
    EJNMMI Physics. 2024; 11(1): 61 (14 pp.). https://doi.org/10.1186/s40658-024-00669-5
    DORA PSI
  • Holzleitner N, Cwojdzinski T, Beck R, Urtz-Urban N, Hillhouse CC, Grundler PV, et al.
    Preclinical evaluation of gastrin-releasing peptide receptor antagonists labeled with 161Tb and 177Lu: a comparative study
    Journal of Nuclear Medicine. 2024; 65(3): 481-484. https://doi.org/10.2967/jnumed.123.266233
    DORA PSI
  • Moiseeva AN, Favaretto C, Talip Z, Grundler PV, van der Meulen NP
    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
  • Müller C, van der Meulen NP
    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)
    In: Shams A, Al-Athel K, Tiselj I, Pautz A, Kwiatkowski T, eds. Challenges and recent advancements in nuclear energy systems. Proceedings of Saudi international conference on nuclear power engineering (SCOPE). Lecture Notes in Mechanical Engineering (LNME). Cham: Springer Nature; 2024:39-44. https://doi.org/10.1007/978-3-031-64362-0_5
    DORA PSI
  • Toyohara J, Vugts D, Kiss OC, Todde S, Li XG, Liu Z, et al.
    Highlight selection of radiochemistry and radiopharmacy developments by editorial board
    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
    EJNMMI Research. 2023; 13(1): 32 (14 pp.). https://doi.org/10.1186/s13550-023-00979-2
    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
    EJNMMI Physics. 2022; 9(1): 19 (18 pp.). https://doi.org/10.1186/s40658-022-00448-0
    DORA PSI
  • Tosato M, Verona M, Favaretto C, Pometti M, Zanoni G, Scopelliti F, et al.
    Chelation of theranostic copper radioisotopes with S-rich macrocycles: from radiolabelling of copper-64 to in vivo investigation
    Molecules. 2022; 27(13): 4158 (19 pp.). https://doi.org/10.3390/molecules27134158
    DORA PSI
  • Alves F, Antunes IF, Cazzola E, Cleeren F, Cornelissen B, Denkova A, et al.
    Highlight selection of radiochemistry and radiopharmacy developments by editorial board
    EJNMMI Radiopharmacy and Chemistry. 2021; 6(1): 31 (16 pp.). https://doi.org/10.1186/s41181-021-00146-9
    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
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