Fluorine‐18 radiolabeling of a nitrophenyl sulfoxide and its evaluation in an SK‐RC‐52 model of tumor hypoxia

The significance of imaging hypoxia with the positron emission tomography ligand ¹⁸F]FMISO has been demonstrated in a variety of cancers. However, the slow kinetics of ¹⁸F]FMISO require a 2‐h delay between tracer administration and patient scanning. Labeled chloroethyl sulfoxides have shown faster kinetics and higher contrast than ¹⁸F]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 K¹⁸F]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 ¹⁸F]1 is retained in hypoxic tumors and has similar hypoxia selectivity to ¹⁸F]FMISO. Because of a three times faster clearance rate than ¹⁸F]FMISO from normoxic tissue, ¹⁸F]1 has emerged as a promising new radiotracer for hypoxia imaging.