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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
Author(s) -
Ackermann Uwe,
Sigmund Duanne,
Yeoh Shinn Dee,
Rigopoulos Angela,
O'Keefe Graeme,
Cartwright Glenn,
White Jonathan,
Scott Andrew M.,
TochonDanguy Henri J.
Publication year - 2011
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.1932
Subject(s) - carbodiimide , chemistry , hydroxymethyl , in vivo , metabolite , yield (engineering) , 1,4 naphthoquinone , total synthesis , high performance liquid chromatography , radiochemistry , positron emission tomography , nuclear chemistry , chromatography , stereochemistry , medicinal chemistry , nuclear medicine , biochemistry , medicine , materials science , microbiology and biotechnology , metallurgy , biology
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.