Reaction of [ 18 F]4‐fluorobenzenediazonium cations with cysteine or the cysteinyl group: preparation of 18 F‐labeled S‐aryl‐cysteine and a radiolabeled peptide

A reaction route for the preparation of no‐carrier‐added (n.c.a.) [ 18 F]S‐4‐fluorophenylcysteine 7 via the [ 18 F]‐4‐fluorobenzenediazonium ion 4 is described. The key step in this radiosynthesis is the reaction of 4 with cysteine forming [ 18 F]4‐fluorophenyldiazocysteine 6 , which is subsequently converted into 7 by irradiation with 366 nm light. 4 was synthesized by reacting 1,4‐dinitrobenzene 1 with [ 18 F]‐fluoride in acetonitrile in a PEEK‐capillary in a microwave oven. After dilution of the reaction mixture with methanol, the resulting [ 18 F]4‐fluoro‐1‐nitrobenzene 2 was submitted to reduction by means of H 2 with Pd on C catalyst. The resulting [ 18 F]4‐fluoroaniline 3 was purified by HPLC and diazotized to 4 . The preparation of 4 was optimized with regard to yield and purity. The radiochemical yield of 6 was >90% (based on 3 ) while after UV irradiation and HPLC purification 45% of 7 (based on 3 ) was obtained (yields corrected for decay). The suitability of this method for labeling peptides with fluorine‐18 was demonstrated by application to the tripeptide, glutathione (GSH; γ‐L‐glutamyl‐L‐cysteinyglycine) 8 . Copyright © 2002 John Wiley & Sons, Ltd.