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Promising Prospects for Sc-44-/Sc-47-Based Theragnostics: Application of Sc-47 for Radionuclide Tumor Therapy in Mice

Journal article
Authors C. Muller
M. Bunka
S. Haller
U. Koster
V. Groehn
Peter Bernhardt
N. van der Meulen
A. Turler
R. Schibli
Published in Journal of Nuclear Medicine
Volume 55
Issue 10
Pages 1658-1664
ISSN 0161-5505
Publication year 2014
Published at Institute of Clinical Sciences, Department of Radiation Physics
Pages 1658-1664
Language en
Links dx.doi.org/10.2967/jnumed.114.14161...
Keywords Sc-47, radionuclide therapy, SPECT, folate receptor, folic acid, CARRIER-ADDED SC-47, IN-VIVO, CONJUGATE, PET, RADIOPHARMACEUTICALS, RADIOIMMUNOTHERAPY, TISSUES, LU-177, TB-161, ALPHA, Radiology, Nuclear Medicine & Medical Imaging
Subject categories Basic Medicine

Abstract

In recent years, Sc-47 has attracted attention because of its favorable decay characteristics (half-life, 3.35 d; average energy, 162 key; Ey, 159 key) for therapeutic application and for SPECT imaging. The aim of the present study was to investigate the suitability of Sc-47 for radionuclide therapy in a preclinical setting. For this purpose a novel DOTA-folate conjugate (cm10) with an albumin-binding entity was used. Methods: Sc-47 was produced via the Ca-46(n,gamma)Ca-47 -> Sc beta-47 nuclear reaction at the high-flux reactor at the Institut Laue-Langevin. Separation of the Sc-47 from the target material was performed by a semi-automated process using extraction chromatography and cation exchange chromatography. Sc-47-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 Sc-47-cm10 (10 MBq) or only saline. Tumor growth and survival time were compared between the two groups of mice. Results: Irradiation of Ca-46 resulted in approximately 1.8 GBq of Ca-47, which subsequently decayed to Sc-47. Separation of Sc-47 from Ca-47 was obtained with 80% yield in only 10 min. The Sc-47 was then available in a small volume (-500 pL) of an ammonium acetate/HCI (pH 4.5) solution suitable for direct radiolabeling. Sc-47-cm10 was prepared with a radiochemical yield of more than 96% at a specific activity of up to 13 MBq/nmol. In vitro 475ccm10 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 Sc-47-cm10 (10 MBq, 10 Gy) resulting in a more than 50% increase in survival time, compared with untreated control mice. Conclusion: With this study, we demonstrated the suitability of using Sc-47 for therapeutic purposes. On the basis of our recent results obtained with Sc-44-folate, the present work confirms the applicability of Sc-44/Sc-47 as an excellent matched pair of nuclides for PET imaging and radionuclide therapy.

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