Abstract: The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D2-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D2-receptor affinities for all compounds in the nanomolar range (Ki(SiFA-DMFP) = 13.6 nM, Ki(SiFA-FP) = 33.0 nM, Ki(SiFA-DDMFP) = 62.7 nM and Ki(SiFA-M-FP) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with [18F]fluoride/TBAHCO3 in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/µmol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min.
Keywords: fluorine; isotopic labeling; positron emission tomography; radiopharmaceuticals; silicon
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Iovkova-Berends, L.; Wängler, C.; Zöller, T.; Höfner, G.; Wanner, K.T.; Rensch, C.; Bartenstein, P.; Kostikov, A.; Schirrmacher, R.; Jurkschat, K.; Wängler, B. t-Bu2SiF-Derivatized D2-Receptor Ligands: The First SiFA-Containing Small Molecule Radiotracers for Target-Specific PET-Imaging. Molecules 2011, 16, 7458-7479.
Iovkova-Berends L, Wängler C, Zöller T, Höfner G, Wanner KT, Rensch C, Bartenstein P, Kostikov A, Schirrmacher R, Jurkschat K, Wängler B. t-Bu2SiF-Derivatized D2-Receptor Ligands: The First SiFA-Containing Small Molecule Radiotracers for Target-Specific PET-Imaging. Molecules. 2011; 16(9):7458-7479.
Iovkova-Berends, Ljuba; Wängler, Carmen; Zöller, Thomas; Höfner, Georg; Wanner, Klaus Theodor; Rensch, Christian; Bartenstein, Peter; Kostikov, Alexey; Schirrmacher, Ralf; Jurkschat, Klaus; Wängler, Björn. 2011. "t-Bu2SiF-Derivatized D2-Receptor Ligands: The First SiFA-Containing Small Molecule Radiotracers for Target-Specific PET-Imaging." Molecules 16, no. 9: 7458-7479.