title: Synthesis and Evaluation of Astatinated N-[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates.
abstract: 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.
authors.affiliation: Department of Radiation Physics, Gothenburg University , Gula Stråket 2B, 41345 Gothenburg, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Aneheim
authors.affiliation: Department of Radiation Physics, Gothenburg University , Gula Stråket 2B, 41345 Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Gustafsson
authors.affiliation: Department of Oncology, Gothenburg University , 41345 Gothenburg, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Albertsson
authors.affiliation: Department of Radiation Physics, Gothenburg University , Gula Stråket 2B, 41345 Gothenburg, Sweden.
authors.forename: Tom
authors.initials: T
authors.lastname: Bäck
authors.affiliation: PET and Cyclotron Unit, KF3982, Copenhagen University Hospital , DK-2100 Copenhagen, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Department of Radiation Physics, Gothenburg University , Gula Stråket 2B, 41345 Gothenburg, Sweden.
authors.forename: Stig
authors.initials: S
authors.lastname: Palm
authors.affiliation: Department of Applied Physics, Chalmers University of Technology , 41296, Gothenburg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Svedhem
authors.affiliation: Department of Radiation Physics, Gothenburg University , Gula Stråket 2B, 41345 Gothenburg, Sweden.
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
mesh_terms: D000818:Animals; D001246:Astatine / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry*; D018796:Immunoconjugates / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D001549:Benzamides; D018796:Immunoconjugates; D001246:Astatine