Therapeutic Potential of 47Sc in Comparison to 177Lu and 90Y: Preclinical Investigations

Research output: Contribution to journalArticle

Authors

  • Klaudia Siwowska
  • Patrycja Guzik
  • Katharina A. Domnanich
  • Josep M. Monné Rodriguez
  • Peter Bernhardt
  • Bernard Ponsard
  • Roger Hasler
  • Francesca Borgna
  • Roger Schibli
  • Ulli Köster
  • Nicholas P. van der Meulen
  • Cristina Müller

Institutes & Expert groups

  • PSI - Paul Scherrer Institute
  • UB - University of Bern
  • UZH - Universität Zurich/University of Zurich
  • University of Gothenburg - Sahlgren Academy - Institute of Clinical Sciences
  • Sahlgrenska University Hospital
  • ILL - Institut Laue Langevin
  • ETHZ - Eidgenösslsche Technische Hochshule Zürich

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Abstract

Targeted radionuclide therapy with 177Lu- and 90Y-labeled radioconjugates is a clinicallyestablished treatment modality for metastasized cancer. 47Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy 蚠-particles. In this study, 47Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of 177Lu-folate and 90Y-folate, respectively. In vitro, 47Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to 177Lu-folate, but 90Y-folate was more potent at equal activities due to the higher energy of emitted 蚠-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with 47Sc-folate (12.5MBq), 177Lu-folate (10MBq), and 90Y-folate (5MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, 47Sc is likely to be comparable to 177Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with 44Sc or 43Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.

Details

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalPharmaceutics
Volume11
Issue number8
DOIs
Publication statusPublished - 20 Aug 2019

Keywords

  • Radionucliede therapy, SPECT, folate receptor, DOTA-folate, IGROV-1 tumor xenografts, preclinical therapy, 177-Lu, 47-Sc, 90Y

ID: 5550788