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Molecule of the month - TE-TDDPN = 6-O-(2-(tosyloxyethyl)-6-O-desmethyl-3-O-trityl-diprenorphine

Welcome to our next molecule of the month 2024 - TE-TDDPN 
A relatively complex synthesis complicates use of the popular opioid receptor radiotracer 6-O-(2-[18F]fluoroethyl)-6-O-desmethyl-diprenorphine ([18F]FE-DPN) for positron emission tomography (PET) studies. To simplify access to [18F]FE-DPN, the novel precursor TE-TDDPN was developed for direct one-pot, two-step nucleophilic radiosynthesis of the PET tracer [1]. Several groups demonstrated successful application of the new precursor [2,3,4]. In honour of the memory of Professor Gjermund Henriksen, his life work, and his many contributions to the field of PET imaging of opioid receptors, TE-TDDPN was named as “Henriksen precursor”.

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[1] Marton, J. et al. A New Precursor for the Radiosynthesis of 6-O-(2[¹⁸F]Fluoroethyl)-6-O-Desmethyl-Diprenorphine ([¹⁸F]FE-DPN) by Nucleophilic Radiofluorination. Lett. Org. Chem. 2021, 18, 344–352.

[2] Levinstein, M. R. et al. 6-O-(2-[18F]Fluoroethyl)-6-O-desmethyl-diprenorphine ([18F]FE-DPN) preferentially binds to mu opioid receptors in vivo. Mol. Imag. Biol. 2023, 25, 2, 384–390.

[3] Németh, E. et al. Optimization of a nucleophilic two-step radiosynthesis of 6-O-(2-[18F]fluoroethyl)-6-O-desmethyl-diprenorphine ([18F]FE-DPN) for PET imaging of brain opioid receptors. Int. J. Mol. Sci. 2023, 24, 17, 13152.

[4] Bettcher, B. et al. [18F]-FE-DPN 6-O-(2-[18F]fluoroethyl)-6-O-desmethyl-diprenorphine with Dynamic PET Imaging for Brain µ-Opioid Receptors in Nonhuman Primate Models, XIV International Symposium on Functional NeuroReceptor Mapping of the Living Brain, Montreal, Canada, 18-21th May, 2024.