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Radiosynthesis of 2‐ exo ‐(2′‐[ 18 F]Fluoro‐3′‐(4‐fluorophenyl)‐pyridin‐5′‐yl)‐7‐azabicyclo[2.2.1]heptane ([ 18 F]F 2 PhEP), a potent epibatidine‐based radioligand for nicotinic acetylcholine receptor PET imaging
Author(s) -
Roger Gaëlle,
Hinnen Françoise,
Valette Héric,
Saba Wadad,
Bottlaender Michel,
Dollé Frédéric
Publication year - 2006
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.1063
Subject(s) - radiosynthesis , chemistry , epibatidine , radioligand , nicotinic acetylcholine receptor , heptane , yield (engineering) , nucleophile , high performance liquid chromatography , bicyclic molecule , medicinal chemistry , nicotinic agonist , nuclear chemistry , stereochemistry , organic chemistry , in vivo , receptor , metallurgy , biology , catalysis , biochemistry , materials science , microbiology and biotechnology
2‐ exo ‐(2′‐Fluoro‐3′‐(4‐fluorophenyl)‐pyridin‐5′‐yl)‐7‐azabicyclo[2.2.1]heptane (F 2 PhEP), a novel, epibatidine‐based, α4β2‐selective nicotinic acetylcholine receptor antagonist of low toxicity, as well as the corresponding N‐ Boc‐protected chloro‐ and bromo derivatives as precursors for labelling with fluorine‐18 were synthesized from 7‐ tert ‐butoxycarbonyl‐7‐azabicyclo[2.2.1]hept‐2‐ene in 13, 19 and 8% overall yield, respectively. [ 18 F]F 2 PhEP was prepared in 8–9% overall yield (non‐decay‐corrected) using 1 mg of the bromo derivative in the following two‐step radiochemical process: (1) no‐carrier‐added nucleophilic hetero aromatic ortho‐ radiofluorination with the activated K[ 18 F]F‐Kryptofix ® 222 complex in DMSO using microwave activation at 250 W for 90 s, followed by (2) quantitative TFA‐induced removal of the N ‐Boc protective group. Radiochemically pure (>95%) [ 18 F]F 2 PhEP (1.48–1.66 GBq, 74–148 GBq/µmol) was obtained after semi‐preparative HPLC (Symmetry ® C18, eluent aqueous 0.05 M NaH 2 PO 4 CH 3 CN: 78/22 (v:v)) in 75–80 min starting from an 18.5 GBq aliquot of a cyclotron‐produced [ 18 F]fluoride production batch. Copyright © 2006 John Wiley & Sons, Ltd.