• DOI:10.1111/jnc.13716
• Corpus ID: 20626659

Discovery of a fluorinated 4‐oxo‐quinoline derivative as a potential positron emission tomography radiotracer for imaging cannabinoid receptor type 2

@article{Slavik2016DiscoveryOA,
  title={Discovery of a fluorinated 4‐oxo‐quinoline derivative as a potential positron emission tomography radiotracer for imaging cannabinoid receptor type 2},
  author={Roger Slavik and Adrienne M{\"u}ller Herde and Ahmed Haider and Stefanie D. Kr{\"a}mer and Markus Weber and Roger Schibli and Simon M. Ametamey and Linjing Mu},
  journal={Journal of Neurochemistry},
  year={2016},
  volume={138}
}

• R. Slavik, Adrienne Müller Herde, +5 authors L. Mu
• Published 1 July 2016
• Biology, Chemistry
• Journal of Neurochemistry

The cannabinoid receptor type 2 (CB2) is part of the endocannabinoid system and has gained growing attention in recent years because of its important role in neuroinflammatory/neurodegenerative diseases. Recently, we reported on a carbon‐11 labeled 4‐oxo‐quinoline derivative, designated RS‐016, as a promising radiotracer for imaging CB2 using PET. In this study, three novel fluorinated analogs of RS‐016 were designed, synthesized, and pharmacologically evaluated. The results of our efforts led to the identification of N‐(1‐adamantyl)‐1‐(2‐(2‐fluoroethoxy)ethyl)‐8‐methoxy‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxamide (RS‐126) as the most potent candidate for evaluation as a CB2 PET ligand. [18F]RS‐126 was obtained in ≥ 99% radiochemical purity with an average specific radioactivity of 98 GBq/μmol at the end of the radiosynthesis. [18F]RS‐126 showed a logD7.4 value of 1.99 and is stable in vitro in rat and human plasma over 120 min, whereas 55% intact parent compound was found in vivo in rat blood plasma at 10 min post injection. In vitro autoradiographic studies with CB2‐positive rat spleen tissue revealed high and blockable binding which was confirmed in in vivo displacement experiments with rats by dynamic PET imaging. Ex vivo biodistribution studies confirmed accumulation of [18F]RS‐126 in rat spleen with a specificity of 79% under blocking conditions. The moderate elevated CB2 levels in LPS‐treated mice brain did not permit the detection of CB2 by [18F]RS‐126 using PET imaging. In summary, [18F]RS‐126 demonstrated high specificity toward CB2 receptor in vitro and in vivo and is a promising radioligand for imaging CB2 receptor expression.