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Synthesis and Evaluation of Astatinated N-[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates

Artikel i vetenskaplig tidskrift
Författare Emma Aneheim
Anna Gustafsson
Per Albertsson
Tom Bäck
Holger Jensen
Stig Palm
Sofia Svedhem
Sture Lindegren
Publicerad i Bioconjugate chemistry
Volym 27
Nummer/häfte 3
Sidor 688-97
ISSN 1520-4812
Publiceringsår 2016
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Sidor 688-97
Språk en
Länkar dx.doi.org/10.1021/acs.bioconjchem....
Ämneskategorier Cancer och onkologi, Radiofysik

Sammanfattning

Effective treatment of metastasis is a great challenge in the treatment of different types of cancers. Targeted alpha therapy utilizes the short tissue range (50-100 μm) of α particles, making the method suitable for treatment of disseminated occult cancers in the form of microtumors or even single cancer cells. A promising radioactive nuclide for this type of therapy is astatine-211. Astatine-211 attached to tumor-specific antibodies as carrier molecules is a system currently under investigation for use in targeted alpha therapy. In the common radiolabeling procedure, astatine is coupled to the antibody arbitrarily on lysine residues. By instead coupling astatine to disulfide bridges in the antibody structure, the immunoreactivity of the antibody conjugates could possibly be increased. Here, the disulfide-based conjugation was performed using a new coupling reagent, maleimidoethyl 3-(trimethylstannyl)benzamide (MSB), and evaluated for chemical stability in vitro. The immunoconjugates were subsequently astatinated, resulting in both high radiochemical yield and high specific activity. The MSB-conjugate was shown to be stable with a long shelf life prior to the astatination. In a comparison of the in vivo distribution of the new immunoconjugate with other tin-based immunoconjugates in tumor-bearing mice, the MSB conjugation method was found to be a viable option for successful astatine labeling of different monoclonal antibodies.

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