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Updated: Dec 12, 2025

Autoradiography as a Simple and Powerful Method for Visualization and Characterization of Pharmacological Targets
Published on: March 12, 2019
Pharmacological Characterization of Low-to-Moderate Affinity Opioid Receptor Agonists and Brain Imaging with
Julian Ott1, Mona M Spilhaug2, Simone Maschauer1
1Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Translational Research Center, Friedrich Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 12, D-91054 Erlangen, Germany.
Abstract:
The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for 18F-positron emission tomography (18F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacological parameters of 15 candidates were investigated. Two promising compounds 3b and 3e with μ-OR (MOR) selective agonist activity in the moderate range (EC50 = 1-100 nM) were subjected to 18F-fluorination, autoradiography, and small-animal PET imaging. Radioligands [18F]3b and [18F]3e were obtained in activity yields of 21 ± 5 and 23 ± 4% and molar activities of 25-40 and 200-300 GBq/μmol, respectively. Displaceable binding matching MOR distribution in the brain was confirmed by imaging. Radioligands showed a rapid pharmacokinetic profile; however, metabolite-corrected, blood-based modeling was required for data analysis. Observed BPND was low, although treatment with naloxone leads to a marked decrease in specific binding, confirming the discovery of a new template for 18F-labeled OR-agonist PET ligands.
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