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Open AccessArticle

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

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Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland
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Laboratory of Radiochemistry, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland
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Department of Chemistry and Biochemistry University of Bern, 3012 Bern, Switzerland
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Laboratory for Animal Model Pathology (LAMP), Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
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Department of Radiation Physics, The Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden
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Department of Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
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SCK.CEN, Belgian Nuclear Research Centre, BR2 Reactor, 2400 Mol, Belgium
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Department of Chemistry and Applied Biosciences, ETH Zurich, 8092 Zurich, Switzerland
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Institut Laue Langevin, 38042 Grenoble, France
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Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(8), 424; https://doi.org/10.3390/pharmaceutics11080424
Received: 14 July 2019 / Revised: 13 August 2019 / Accepted: 15 August 2019 / Published: 20 August 2019
(This article belongs to the Special Issue Targeted Radionuclide Tumor Therapy)
Targeted radionuclide therapy with 177Lu- and 90Y-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. 47Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy β-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 β-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with 47Sc-folate (12.5 MBq), 177Lu-folate (10 MBq), and 90Y-folate (5 MBq), 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. View Full-Text
Keywords: 47Sc; 177Lu; 90Y; radionuclide therapy; SPECT; folate receptor; DOTA-folate; IGROV-1 tumor xenografts; preclinical therapy 47Sc; 177Lu; 90Y; radionuclide therapy; SPECT; folate receptor; DOTA-folate; IGROV-1 tumor xenografts; preclinical therapy
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MDPI and ACS Style

Siwowska, K.; Guzik, P.; Domnanich, K.A.; Monné Rodríguez, J.M.; Bernhardt, P.; Ponsard, B.; Hasler, R.; Borgna, F.; Schibli, R.; Köster, U.; van der Meulen, N.P.; Müller, C. Therapeutic Potential of 47Sc in Comparison to 177Lu and 90Y: Preclinical Investigations. Pharmaceutics 2019, 11, 424.

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