Fluorine‐18 radiolabeling of a nitrophenyl sulfoxide and its evaluation in an SK‐RC‐52 model of tumor hypoxia |
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Authors: | Evelyn Laurens Shinn Dee Yeoh Angela Rigopoulos Graeme J O'Keefe Henri J Tochon‐Danguy Lee Wenn Chong Jonathan M White Andrew M Scott Uwe Ackermann |
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Institution: | 1. School of Chemistry, The University of Melbourne, Melbourne, Australia;2. Bio21 Institute, The University of Melbourne, Melbourne, Australia;3. Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia;4. Olivia Newton‐John Cancer Research Institute, Melbourne, Australia;5. Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia;6. School of Cancer Medicine, La Trobe University, Melbourne, Australia |
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Abstract: | 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. |
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Keywords: | hypoxia radiolabeling SK‐RC‐52 tumor model small animal imaging |
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