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

Bioorganic & Medicinal Chemistry
Torsten KniessJens Pietzsch

Abstract

The radiosynthesis of 3-(4-[(18)F]fluorophenyl)-2-(4-methylsulfonylphenyl)-1H-indole [(18)F]-3 as potential PET radiotracer for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo is described. [(18)F]-3 was prepared by McMurry cyclization of a (18)F-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 [(18)F]-3 was synthesized in 80 min synthesis time in 10% total decay corrected yield from [(18)F]fluoride in radiochemical purity >98% and a specific activity of 74-91 GBq/μmol (EOS). [(18)F]-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 [(18)F]-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 [(18)F]-3 could be observed by dynamic small animal PET studies on HT-29 tumor-...Continue Reading

References

Sep 17, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shahar Lev-AriNadir Arber
Jan 1, 2010·Carcinogenesis·James J LeeHiroshi Nakagawa
Dec 29, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·Maria Teresa Rizzo

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Citations

Oct 12, 2012·Amino Acids·Nadine TandlerJens Pietzsch
Jun 14, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Markus LaubeJens Pietzsch
Feb 1, 2015·Biochemical and Biophysical Research Communications·Christoph TonderaJens Pietzsch
Mar 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mathias KranzJens Pietzsch
Feb 22, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christin NeuberJens Pietzsch
Oct 23, 2013·Organic & Biomolecular Chemistry·Ole TietzFrank Wuest
Jan 29, 2014·Journal of Labelled Compounds & Radiopharmaceuticals·A PacelliG Smith
Apr 15, 2017·Oncotarget·Agnieszka MorgenrothBoris D Zlatopolskiy
Oct 28, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Markus LaubeJens Pietzsch
Jul 25, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Joseph LauFrançois Bénard

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