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

Artikel i vetenskaplig tidskrift
Författare C. Muller
M. Bunka
S. Haller
U. Koster
V. Groehn
Peter Bernhardt
N. van der Meulen
A. Turler
R. Schibli
Publicerad i Journal of Nuclear Medicine
Volym 55
Nummer/häfte 10
Sidor 1658-1664
ISSN 0161-5505
Publiceringsår 2014
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Sidor 1658-1664
Språk en
Länkar dx.doi.org/10.2967/jnumed.114.14161...
Ämnesord 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
Ämneskategorier Medicinska grundvetenskaper

Sammanfattning

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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