title: Promising prospects for 44Sc-/47Sc-based theragnostics: application of 47Sc for radionuclide tumor therapy in mice.
abstract: In recent years, (47)Sc has attracted attention because of its favorable decay characteristics (half-life, 3.35 d; average energy, 162 keV; Eγ, 159 keV) for therapeutic application and for SPECT imaging. The aim of the present study was to investigate the suitability of (47)Sc for radionuclide therapy in a preclinical setting. For this purpose a novel DOTA-folate conjugate (cm10) with an albumin-binding entity was used.
  
  
  METHODS
  (47)Sc was produced via the (46)Ca(n,γ)(47)Ca[Formula: see text](47)Sc nuclear reaction at the high-flux reactor at the Institut Laue-Langevin. Separation of the (47)Sc from the target material was performed by a semi-automated process using extraction chromatography and cation exchange chromatography. (47)Sc-labeled cm10 was tested on folate receptor-positive KB tumor cells in vitro. Biodistribution and SPECT imaging experiments were performed in KB tumor-bearing mice. Radionuclide therapy was conducted with two groups of mice, which received either (47)Sc-cm10 (10 MBq) or only saline. Tumor growth and survival time were compared between the two groups of mice.
  
  
  RESULTS
  Irradiation of (46)Ca resulted in approximately 1.8 GBq of (47)Ca, which subsequently decayed to (47)Sc. Separation of (47)Sc from (47)Ca was obtained with 80% yield in only 10 min. The (47)Sc was then available in a small volume (∼500 μL) of an ammonium acetate/HCl (pH 4.5) solution suitable for direct radiolabeling. (47)Sc-cm10 was prepared with a radiochemical yield of more than 96% at a specific activity of up to 13 MBq/nmol. In vitro (47)Sc-cm10 showed folate receptor-specific binding and uptake into KB tumor cells. In vivo SPECT/CT images allowed the visualization of accumulated radioactivity in KB tumors and in the kidneys. The therapy study showed a significantly delayed tumor growth in mice, which received (47)Sc-cm10 (10 MBq, 10 Gy) resulting in a more than 50% increase in survival time, compared with untreated control mice.
  
  
  CONCLUSIONS
  With this study, we demonstrated the suitability of using (47)Sc for therapeutic purposes. On the basis of our recent results obtained with (44)Sc-folate, the present work confirms the applicability of (44)Sc/(47)Sc as an excellent matched pair of nuclides for PET imaging and radionuclide therapy.
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland cristina.mueller@psi.ch.
authors.forename: Cristina
authors.initials: C
authors.lastname: Müller
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry University of Bern, Bern, Switzerland.
authors.forename: Maruta
authors.initials: M
authors.lastname: Bunka
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Haller
authors.affiliation: Institut Laue-Langevin, Grenoble, France.
authors.forename: Ulli
authors.initials: U
authors.lastname: Köster
authors.affiliation: Merck and Cie, Schaffhausen, Switzerland.
authors.forename: Viola
authors.initials: V
authors.lastname: Groehn
authors.affiliation: Department of Radiation Physics, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Medical Physics and Medical Bioengeneering, Sahlgrenska University Hospital, Gothenburg, Sweden; and.
authors.forename: Peter
authors.initials: P
authors.lastname: Bernhardt
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Nicholas
authors.initials: N
authors.lastname: van der Meulen
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry University of Bern, Bern, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Türler
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
mesh_terms: D000818:Animals; D002132:Calcium Radioisotopes / Q000378:metabolism; D045744:Cell Line, Tumor; D002852:Chromatography, Ion Exchange; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D049268:Positron-Emission Tomography / Q000379:methods; D011878:Radiotherapy / Q000379:methods*; D012538:Scandium / Q000737:chemistry* / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D002132:Calcium Radioisotopes; D058973:Folate Receptors, GPI-Anchored; D012538:Scandium
keywords: 47Sc; SPECT; folate receptor; folic acid; radionuclide therapy