Synthesis of 2‐[(4‐[ 18 F]Fluorobenzoyloxy)methyl]‐1,4‐naphthalenedione from 2‐hydroxymethyl 1,4‐naphthoquinone and 4‐[ 18 F]fluorobenzoic acid using dicyclohexyl carbodiimide

2‐[(4‐[ 18 F]Fluorobenzoyloxy)methyl]‐1,4‐naphthalenedione ([ 18 F] 1 ) was synthesised as a putative hypoxia imaging agent from 2‐hydroxymethyl 1,4‐naphthoquinone ( 7 ) and 4‐[ 18 F]fluorobenzoic acid ([ 18 F] 8 ) using dicyclohexyl carbodiimide (DCC) to activate [ 18 F] 8 . This coupling reaction was fast and gave quantitative yields. Further investigations are warranted on the use of DCC as a coupling agent in Positron Emission Tomography. The synthesis including HPLC purification and reformulation has been fully automated on a modified FDG synthesiser with two reactor vials. [ 18 F] 1 was produced in a radiochemical yield of 27 ± 5%, with a radiochemical purity of 97.5% and a specific activity of 78.4–134.5 GBq/µmol at the end of synthesis ( n  = 23). The total synthesis time including reformulation was 65 min. [ 18 F] 1 was found to be stable in plasma and saline, but underwent rapid metabolism in a phase 1 metabolite assay using rat S9 liver fractions. An in vivo evaluation of [ 18 F] 1 in transplanted, hypoxic SK‐RC‐52 tumour‐bearing BALB/c nude mice revealed the tumour‐to‐muscle ratio to be 2.4 ± 0.1 at 2 h post‐injection. Copyright © 2011 John Wiley & Sons, Ltd.