Radiosynthesis of 2-exo-(2′-[18F]Fluoro-3′-(4-fluorophenyl)-pyridin-5′-yl)-7-azabicyclo[2.2.1]heptane ([18F]F2PhEP), a potent epibatidine-based radioligand for nicotinic acetylcholine receptor PET imaging

✍ Scribed by Gaëlle Roger; Françoise Hinnen; Héric Valette; Wadad Saba; Michel Bottlaender; Frédéric Dollé

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: French
• Weight: 189 KB
• Volume: 49
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1063

✦ Synopsis

2-exo-(2 0 -Fluoro-3 0 -(4-fluorophenyl)-pyridin-5 0 -yl)-7-azabicyclo[2.2.1]heptane (F 2 PhEP), a novel, epibatidine-based, a4b2-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-tertbutoxycarbonyl-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 heteroaromatic ortho-radiofluorination with the activated K[ 18 F]F-Kryptofix 1 222 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/mmol) was obtained after semi-preparative HPLC (Symmetry 1 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