Synthesis and preclinical evaluation of fluorinated 5-azaindoles as CB2 PET radioligands

Annukka Kallinen, Karine Mardon, Samuel Lane, Andrew P. Montgomery, Rajiv Bhalla, Damion H. R. Stimson, Muneer Ahamed, Gary J. Cowin, David Hibbs, Eryn L. Werry, Roger Fulton, Mark Connor, Michael Kassiou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Several classes of cannabinoid receptor type 2 radioligands have been evaluated for imaging of neuroinflammation, with successful clinical translation yet to take place. Here we describe the synthesis of fluorinated5-azaindoles and pharmacological characterization and in vivo evaluation of 18F-radiolabeled analogues. [18F]2 (hCB2 Ki = 96.5 nM)and [18F]9 (hCB2 Ki = 7.7 nM) were prepared using Cu-mediated 18F-fluorinationwith non-decay-corrected radiochemical yields of 15 ± 6% and18 ± 2% over 85 and 80 min, respectively, with high radiochemical purities (>97%) and molar activities (140-416 GBq/μmol). In PET imaging studies in rats, both [18F]2 and [18F]9 demonstrated specific binding in CB2-rich spleen after pretreatment with CB2-specific GW405833.Moreover, [18F]9 exhibited higher brain uptake at later time points in a murine model of neuroinflammation compared with a healthy control group. The results suggest further evaluation of azaindole based CB2 radioligands is warranted in other neuroinflammation models.

Original languageEnglish
Pages (from-to)2902-2921
Number of pages20
JournalACS Chemical Neuroscience
Issue number16
Publication statusPublished - 16 Aug 2023


  • aryl boronate
  • CB2 radioligand
  • Cu-mediatedfluorination
  • fluorine-18
  • LPS
  • neuroinflammation


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