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Fluorine‐18 radiolabeling of a nitrophenyl sulfoxide and its evaluation in an SK‐RC‐52 model of tumor hypoxia
Author(s) -
Laurens Evelyn,
Yeoh Shinn Dee,
Rigopoulos Angela,
O'Keefe Graeme J.,
TochonDanguy Henri J.,
Chong Lee Wenn,
White Jonathan M.,
Scott Andrew M.,
Ackermann Uwe
Publication year - 2016
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.3426
Subject(s) - chemistry , sulfoxide , hypoxia (environmental) , fluorine , radiochemistry , combinatorial chemistry , organic chemistry , oxygen
The significance of imaging hypoxia with the positron emission tomography ligand [ 18 F]FMISO has been demonstrated in a variety of cancers. However, the slow kinetics of [ 18 F]FMISO require a 2‐h delay between tracer administration and patient scanning. Labeled chloroethyl sulfoxides have shown faster kinetics and higher contrast than [ 18 F]FMISO in a rat model of ischemic stroke. However, these nitrogen mustard analogues are unsuitable for routine production and use in humans. Here, we report on the synthesis and in vitro and in vivo evaluation of a novel sulfoxide, which contains an ester moiety for hydrolysis and subsequent trapping in hypoxic cells. Non‐decay corrected yields of radioactivity were 1.18 ± 0.24% ( n = 27, 2.5 ± 0.5% decay corrected radiochemical yield) based on K[ 18 F]F. The radiotracer did not show any defluorination and did not undergo metabolism in an in vitro assay using S9 liver fractions. Imaging studies using an SK‐RC‐52 tumor model in BALB/c nude mice have revealed that [ 18 F]1 is retained in hypoxic tumors and has similar hypoxia selectivity to [ 18 F]FMISO. Because of a three times faster clearance rate than [ 18 F]FMISO from normoxic tissue, [ 18 F]1 has emerged as a promising new radiotracer for hypoxia imaging.