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 K[18F]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. A new nitrophenyl sulfoxide for imaging hypoxia was synthesized via halogen exchange in non‐decay corrected yields of radioactivity of 1.18 ± 0.24%. The radiotracer was investigated in our well‐established SK‐RC‐52 model of tumor hypoxia and its pharmacokinetics compared with [18F]FMISO. The fast clearance of [18F]1 from normoxic tissue allows for imaging at earlier timepoints than [18F]FMISO. This compound is an interesting lead structure for further development of hypoxia tracers.