Radiosynthesis of [18F]LBT‐999, a selective radioligand for the visualization of the dopamine transporter with PET

LBT‐999 (8‐((E)‐4‐fluoro‐but‐2‐enyl)‐3β‐p‐tolyl‐8‐aza‐bicyclo[3.2.1]octane‐2β‐carboxylic acid methyl ester) is a cocaine derivative belonging to a new generation of highly selective dopamine transporter ligands (K_D:9 nM). LBT‐999 was labelled with fluorine‐18 at its fluoromethylvinyl moiety using the following two‐step radiochemical process: (a) No‐carrier‐added nucleophilic aliphatic radiofluorination from (E)‐1, 4‐ditosyloxybut‐2‐ene and the activated K[¹⁸F]F‐Kryptofix^®222 complex in acetonitrile at 70°C for 10 min giving (E)‐1‐[¹⁸F]fluoro‐4‐tosyloxybut‐2‐ene, followed by (b) condensation of the latter with 3β‐p‐tolyl‐8‐aza‐bicyclo[3.2.1]octane‐2β‐carboxylic acid methyl ester in N,N‐dimethylformamide containing potassium iodide for 20 min at 90°C and (c) HPLC purification (SunFire? C18, eluent H₂O/CH₃CN/TFA (72:28:0.1 (v/v/v)). Radiochemically pure (> 95%) [¹⁸F]LBT‐999 (2.03–2.96 GBq, 37–111 GBq/μmol) was obtained in 95–100 min starting from a 44.4 GBq [¹⁸F]fluoride ion production batch (4.6–6.7% non‐decay‐corrected overall yield). Copyright © 2006 John Wiley & Sons, Ltd.