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Synthesis, radiofluorination, and preliminary evaluation of the potential 5‐HT 2A receptor agonists [ 18 F]Cimbi‐92 and [ 18 F]Cimbi‐150
Author(s) -
Edgar Fraser Graeme,
Hansen Hanne D.,
LethPetersen Sebastian,
Ettrup Anders,
Kristensen Jesper L.,
Knudsen Gitte M.,
Herth Matthias M.
Publication year - 2017
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3557
Subject(s) - chemistry , agonist , labelling , in vivo , radiochemistry , radiosynthesis , striatum , receptor , pet imaging , biodistribution , 5 ht receptor , radioligand , specific activity , in vitro , serotonin , positron emission tomography , nuclear medicine , biochemistry , neuroscience , psychology , dopamine , medicine , microbiology and biotechnology , biology , enzyme
An agonist PET tracer is of key interest for the imaging of the 5‐HT 2A receptor, as exemplified by the previously reported success of [ 11 C]Cimbi‐36. Fluorine‐18 holds several advantages over carbon‐11, making it the radionuclide of choice for clinical purposes. In this respect, an 18 F‐labelled agonist 5‐HT 2A receptor (5‐HT 2A R) tracer is highly sought after. Herein, we report a 2‐step, 1‐pot labelling methodology of 2 tracer candidates. Both ligands display high in vitro affinities for the 5‐HT 2A R. The compounds were synthesised from easily accessible labelling precursors, and radiolabelled in acceptable radiochemical yields, sufficient for in vivo studies in domestic pigs. PET images partially conformed to the expected brain distribution of the 5‐HT 2A R; a notable exception however being significant uptake in the striatum and thalamus. Additionally, a within‐scan displacement challenge with a 5‐HT 2A R antagonist was unsuccessful, indicating that the tracers cannot be considered optimal for neuroimaging of the 5‐HT 2A R.