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Published Online: 16 February 2015

Shelf-Life of ɛ-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugates, Precursors for 211At Labeling of Antibodies

Publication: Cancer Biotherapy and Radiopharmaceuticals
Volume 30, Issue Number 1

Abstract

Astatine-211 is possibly the most promising radionuclide for targeted α-particle therapy when it comes to the treatment of occult disseminated cancer. Preclinical research has proven effective, and patient studies have been initiated based on these results. However, a lack of production capacity and the complex radiochemistry of 211At are major obstacles for research and prospective clinical applications. In the present study, astatination of immunoconjugates, already prepared well in advance before radiolabeling, was performed to investigate the possibility of formulating a kit-like reagent for the production of 211At radiopharmaceuticals. The shelf-life of ɛ-lysyl-3-(trimethylstannyl)benzamide immunoconjugates was evaluated, that is, the effect of different storage times on the quality of the immunoconjugates. The quality being referred to is the capacity to maintain a good radiochemical yield and good cell-binding property after labeling with 211At. The stability of the conjugates was found to be pH dependent with high stability at pH≥7 and less stability at pH≤5.5. The immunoconjugates (based on trastuzumab) could be kept for more than 3 months in a phosphate buffered saline solution (pH 7.4) at 4°C before labeling, without compromising the quality of the labeled product. The conjugates are also unaffected by storage at −20°C. Conjugates with a good shelf-life compatible with distant shipping as well as improved radiochemistry are important steps to facilitate further clinical progress with 211At.

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Published In

cover image Cancer Biotherapy and Radiopharmaceuticals
Cancer Biotherapy and Radiopharmaceuticals
Volume 30Issue Number 1February 2015
Pages: 41 - 45
PubMed: 25588020

History

Published online: 16 February 2015
Published in print: February 2015
Published ahead of print: 14 January 2015

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    Authors

    Affiliations

    Emma Aneheim
    Department of Radiation Physics, Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Jenny Halleröd
    Department of Radiation Physics, Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
    Per Albertsson
    Department of Oncology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Holger Jensen
    PET and Cyclotron Unit, KF3982, Copenhagen University Hospital, Copenhagen, Denmark.
    Stellan Holgersson
    Division of Energy and Materials, Department of Biological and Chemical Engineering, Chalmers University of Technology, Göteborg, Sweden.
    Sture Lindegren
    Department of Radiation Physics, Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.

    Notes

    Address correspondence to: Sture Lindegren; Department of Radiation Physics, Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital; Gula Stråket 2B, Göteborg 421 45, Sweden
    E-mail: [email protected]

    Disclosure Statement

    The authors hereby declare that there is no existing conflict of interest, financial or otherwise, concerning the presented data and material of this article.

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