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

  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},
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… 

Identification and Preclinical Development of a 2,5,6-Trisubstituted Fluorinated Pyridine Derivative as a Radioligand for the Positron Emission Tomography Imaging of Cannabinoid Type 2 Receptors.

Results suggest that [18F]RoSMA-18-d6 is a promising CB2 PET radioligand for clinical translation, which was sensitive in detecting CB2 upregulation in post-mortem human ALS spinal cord tissue by in vitro autoradiography and elegantly corroborated in CB2 knockout mouse spleen.

Synthesis and in vitro evaluation of fluorine-18 benzimidazole sulfones as CB2 PET-radioligands.

The synthesis and pharmacological evaluation of novel fluorinated pyridyl and ethyl sulfone analogues of 2-(tert-butyl)-5-((2-fluoropyridin-4-yl)sulfonyl)-1-(2-methylpentyl)-1H-benzo[d]imidazole (rac-1a) are described, showing low nanomolar potency and excellent selectivity over the CB1 subtype.

Synthesis, Biodistribution and In vitro Evaluation of Brain Permeable High Affinity Type 2 Cannabinoid Receptor Agonists [11C]MA2 and [18F]MA3

The type 2 cannabinoid receptor (CB2) is a member of the endocannabinoid system and is known for its important role in (neuro)inflammation. A PET-imaging agent that allows in vivo visualization of

Preliminary Assessment of the Anti-inflammatory Activity of New Structural Honokiol Analogs with a 4′-O-(2-Fluoroethyl) Moiety and the Potential of Their 18F-Labeled Derivatives for Neuroinflammation Imaging

It is believed that the structure of [18F]F-IV can be optimized by replacing the substituents in the biphenyl core to eliminate these disadvantages and develop new radioligands for imaging activated microglia.

Positron Emission Tomography Imaging of the Endocannabinoid System: Opportunities and Challenges in Radiotracer Development.

The recent development of PET tracers for imaging cannabinoid receptors 1 (CB1R) and 2 (CB2R) as well as the key enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are summarized, particularly focusing on PET neuroimaging applications.

Functionalized Cannabinoid Subtype 2 Receptor Ligands: Fluorescent, PET, Photochromic and Covalent Molecular Probes

An overview of pharmacological and imaging tools such as fluorescent, positron emission tomography (PET), photochromic and covalent selective CB2R ligands used to investigate and explore the unravelled role(s) of CB2Rs are reported.

Radioligands for positron emission tomography imaging of cannabinoid type 2 receptor.

A suitable positron emission tomography radioligand for imaging CB2 would provide an invaluable research tool to explore the role of CB2 receptor expression in inflammatory disorders.

Synthesis and Preliminary Biological Evaluation of Indol-3-yl-oxoacetamides as Potent Cannabinoid Receptor Type 2 Ligands

The preliminary biological evaluation showed that the fluorinated derivative 8 is a potent and selective CB2 ligand with Ki = 6.2 nM.



Synthesis and preliminary evaluation of [18F]-labeled 2-oxoquinoline derivatives for PET imaging of cannabinoid CB2 receptor.

Discovery of a high affinity and selective pyridine analog as a potential positron emission tomography imaging agent for cannabinoid type 2 receptor.

2,5,6-substituted pyridines as a novel class of potential CB2 PET ligands investigated for their potency and binding properties toward human and rodent CB1 and CB2 and 16 is a promising radiotracer for imaging CB2 in rodents.

Labelling and biological evaluation of [(11)C]methoxy-Sch225336: a radioligand for the cannabinoid-type 2 receptor.

Cannabinoid receptor type 2 (CB2)-selective N-aryl-oxadiazolyl-propionamides: synthesis, radiolabelling, molecular modelling and biological evaluation

The synthesized CB2-selective compounds have high affinity towards CB2 and good selectivity against human CB1 and renders them as suitable candidates for molecular imaging studies employing positron emission tomography (PET).

11C-DPA-713: A Novel Peripheral Benzodiazepine Receptor PET Ligand for In Vivo Imaging of Neuroinflammation

11C-DPA-713 represents a suitable alternative to 11C-PK11195 for PET of PBR as a tracer of neuroinflammatory processes induced by neuronal stress and displays a higher signal-to-noise ratio than 10C- PK11195.

Preclinical evaluation of [11C]NE40, a type 2 cannabinoid receptor PET tracer.

Initial Evaluation of 11C-DPA-713, a Novel TSPO PET Ligand, in Humans

This initial study in humans shows that 11C-DPA-713 is a promising ligand for evaluating TSPO binding with PET, and dose-normalized time–activity curves showed that 12C-N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo]pyrimidin-3-yl]-acetamide gives a larger brain signal.