2023/07/27 by Annukka Kallinen, Karine Mardon, Samuel Lane +10 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Cannabis and Cannabinoid Research #Neurotransmitter Receptor Influence on Behavior #Pharmacological Receptor Mechanisms and Effects
paper · doi:10.1021/acschemneuro.3c00345
openalex publication_date 2023/07/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
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 fluorinated 5-azaindoles and pharmacological characterization and in vivo evaluation of 18 F-radiolabeled analogues. [ 18 F] 2 (hCB2 K i = 96.5 nM) and [ 18 F] 9 (hCB2 K i = 7.7 nM) were prepared using Cu-mediated 18 F-fluorination with non-decay-corrected radiochemical yields of 15 ± 6% and 18 ± 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 [ 18 F] 2 and [ 18 F] 9 demonstrated specific binding in CB2-rich spleen after pretreatment with CB2-specific GW405833. Moreover, [ 18 F] 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.