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Development of a Copper-free Click-Radiolabeling for 99mTc-Tricarbonyl Complexes

Schlesinger, M.


Click chemistry, and in particular copper-free click reactions, have gained growing interest in the field of radiopharmaceutical sciences. The 99mTc-tricarbonyl moiety is an excellent precursor for radiolabelling of biomolecules. This master thesis aims at synthesizing two new chelators containing the 2,2’-dipicolylamine (DPA) moiety for 99mTc and investigating the copper-free strain-promoted cycloaddition for the Tc(CO)3-core. The first chelator was based on a tetrafluorophenyl ester and was successfully radiolabeled with [99mTc][Tc(CO)3(H2O)3]+ at 40°C with a a radiochemical conversion (RCC) of 89% after 20 min. The chelator was afforded in a radiochemical purity over 99% after separation using a cartridge. The subsequent conjugation of an amine-functionalized PSMA (prostate-specific membrane antigen) targeting motif was investigated, and the PSMA targeting 99mTc-complex was afforded with an RCC of 23% at 100°C after 150 min. Two other unknown side products were observed. Further in-depth studies are required to optimize the radiolabeling and to identify the formed side-products. For the SPAAC reaction, a 4,8-diazacyclononyne containing the DPA moiety was prepared via the Nicholas reaction. Radiolabeling at 100°C afforded the radiolabeled complex with an RCC of 89% after 30 min. The ensuing SPAAC reaction with an azide-functionalized PSMA motif was studied at three different temperatures. The PSMA targeting 99mTc-complex was afforded selectively at 100°C after 4 hours with an RCC of 89%. No side products were observed. Nonradioactive Re(CO)3-complexes were synthesized and characterized to confirm the 99mTc-complexes. Further modifications of the 4,8-diazacyclononyne could prospectively enable to carry out the radiolabeling under physiological conditions. Continuing in vitro and in vivo experiments are planned.

Keywords: technetium-99m; click reaction; strainpromoted; tricarbonyl complex

  • Master thesis
    Universität Leipzig, 2022
    Mentor: PD Dr. habil. Constantin Mamat
    122 Seiten


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