title: t-Bu2SiF-derivatized D2-receptor ligands: the first SiFA-containing small molecule radiotracers for target-specific PET-imaging.
abstract: The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D(2)-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 D(2)-receptor affinities for all compounds in the nanomolar range (K(i(SiFA-DMFP)) = 13.6 nM, K(i(SiFA-FP)) = 33.0 nM, K(i(SiFA-DDMFP)) = 62.7 nM and K(i(SiFA-M-FP)) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with [(18)F]fluoride/TBAHCO(3) 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.
authors: Department of Inorganic Chemistry II, Faculty of Chemistry, TU Dortmund, Otto-Hahn-Str. 6, 44221 Dortmund, Germany.
authors: Ljuba
authors: L
authors: Iovkova-Berends
authors: Carmen
authors: C
authors: Wängler
authors: Thomas
authors: T
authors: Zöller
authors: Georg
authors: G
authors: Höfner
authors: Klaus Theodor
authors: KT
authors: Wanner
authors: Christian
authors: C
authors: Rensch
authors: Peter
authors: P
authors: Bartenstein
authors: Alexey
authors: A
authors: Kostikov
authors: Ralf
authors: R
authors: Schirrmacher
authors: Klaus
authors: K
authors: Jurkschat
authors: Björn
authors: B
authors: Wängler
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D065127:Dopamine D2 Receptor Antagonists; D005459:Fluorides / Q000138:chemical synthesis* / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D017448:Receptors, Dopamine D2 / Q000737:chemistry; D017655:Silicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001549:Benzamides; D065127:Dopamine D2 Receptor Antagonists; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D017655:Silicon Compounds; C054375:silicon fluoride; D005459:Fluorides