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Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

Rodrigo Teodoro1, Daniel Gündel1, Winnie Deuther-Conrad1

  • 1Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04318 Leipzig, Germany.

International Journal of Molecular Sciences
|August 7, 2021
PubMed

Insights

A new radiotracer, [18F]LU14, has been developed for imaging cannabinoid receptors type 2 (CB2R). This tracer shows high affinity and selectivity, enabling visualization of CB2R in the brain for therapeutic monitoring.

Area of Science:

  • Radiochemistry
  • Molecular Imaging
  • Neuroscience

Background:

  • Cannabinoid receptors type 2 (CB2R) are therapeutic targets for neurodegenerative diseases and cancer.
  • Developing positron emission tomography (PET) radiotracers is crucial for monitoring CB2R-targeted therapies.

Purpose of the Study:

  • To develop and evaluate a novel PET radiotracer, [18F]LU14, for imaging CB2R.
  • To assess the potential of [18F]LU14 for monitoring CB2R density and occupancy in vivo.

Main Methods:

  • Radiosynthesis of cis-[18F]1-(4-fluorobutyl-N-((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([18F]LU14) from a mesylate precursor.
  • In vitro assessment of CB2R binding affinity.
  • In vivo evaluation using PET imaging in a rat model of CB2R overexpression.

Main Results:

  • Successful radiosynthesis of [18F]LU14.
  • High affinity of [18F]LU14 for CB2R.
  • >80% intact tracer in the brain at 30 minutes post-injection.
  • Selective imaging of CB2R in the brain was demonstrated by PET.

Conclusions:

  • [18F]LU14 is a highly affine CB2R radioligand with favorable brain kinetics.
  • This novel tracer shows potential for non-invasive imaging of CB2R in the brain.
  • [18F]LU14 could be valuable for monitoring CB2R-targeted therapies and investigating disease-related changes in CB2R expression.
Keywords:
binding affinitybraincannabinoid receptor type 2fluorine-18 labellingnaphtyrid-2-onepositron emission tomographyradiochemistry

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