1375104-81-6Relevant articles and documents
Radiosynthesis of a 18F-labeled 2,3-diarylsubstituted indole via McMurry coupling for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo
Kniess, Torsten,Laube, Markus,Bergmann, Ralf,Sehn, Fabian,Graf, Franziska,Steinbach, Joerg,Wuest, Frank,Pietzsch, Jens
, p. 3410 - 3421 (2012)
The radiosynthesis of 3-(4-[18F]fluorophenyl)-2-(4- methylsulfonylphenyl)-1H-indole [18F]-3 as potential PET radiotracer for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo is described. [18F]-3 was prepared by McMurry cyclization of a 18F-labeled intermediate with low valent titanium and zinc via a two-step procedure in a remote controlled synthesizer unit including HPLC purification and solid phase extraction. In this way [18F]-3 was synthesized in 80 min synthesis time in 10% total decay corrected yield from [18F]fluoride in radiochemical purity >98% and a specific activity of 74-91 GBq/μmol (EOS). [18F]-3 was evaluated in vitro using pro-inflammatory stimulated THP-1 and COX-2 expressing tumor cell lines (FaDu, A2058, HT-29), where the radiotracer uptake was shown to be consistent with up regulated COX-2 expression. The stability of [18F]-3 was determined by incubation in rat whole blood and plasma in vitro and by metabolite analysis of arterial blood samples in vivo, showing with 75% of original compound after 60 min an acceptable high metabolic stability. However, no substantial tumor accumulation of [18F]-3 could be observed by dynamic small animal PET studies on HT-29 tumor-bearing mice in vivo. This may be due to the only moderate COX-1/COX-2 selectivity of 3 as demonstrated by both cellular and enzymatic cyclooxygenase inhibition assay in vitro. Nevertheless, the new approach first using McMurry cyclization in 18F-chemistry gives access to 18F-labeled diarylsubstituted heterocycles that hold promise as radiolabeled COX-2 inhibitors.
