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Title: Radiolabelling and evaluation of a novel sulfoxide as a PET imaging agent for tumor hypoxia.
Austin Authors: Laurens, Evelyn;Yeoh, Shinn Dee;Rigopoulos, Angela;Cao, Diana;Cartwright, Glenn A;O'Keefe, Graeme J;Tochon-Danguy, Henri J ;White, Jonathan M;Scott, Andrew M ;Ackermann, Uwe 
Affiliation: Centre for PET, Austin Health, Level 1 HSB, 145 Studley Road, Heidelberg VIC 3084, Australia
School of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne VIC 3010, Australia
Ludwig Institute for Cancer Research, Melbourne - Austin Branch, Heidelberg VIC 3084, Australia
School of Chemistry and Bio21 Institute, The University of Melbourne, Parkville VIC 3052, Australia
Issue Date: 12-Mar-2014
Publication information: Nuclear Medicine and Biology 2014; 41(5): 419-25
Abstract: [¹⁸F]FMISO is the most widely validated PET radiotracer for imaging hypoxic tissue. However, as a result of the pharmacokinetics of [¹⁸F]FMISO a 2h wait between tracer administration and patient scanning is required for optimal image acquisition. In order to develop hypoxia imaging agents with faster kinetics, we have synthesised and evaluated several F-18 labelled anilino sulfoxides. In this manuscript we report on the synthesis, in vitro and in vivo evaluation of a novel fluoroethyltriazolyl propargyl anilino sulfoxide. The radiolabelling of the novel tracer was achieved via 2-[¹⁸F]fluoroethyl azide click chemistry. Radiochemical yields were 23 ± 4% based on 2-[¹⁸F]fluoroethyl azide and 7 ± 2% based on K[¹⁸F]F. The radiotracer did not undergo metabolism or defluorination in an in vitro assay using S9 liver fractions. Imaging studies using SK-RC-52 tumors in BALB/c nude mice have indicated that the tracer may have a higher pO₂ threshold than [¹⁸F]FMISO for uptake in hypoxic tumors. Although clearance from muscle was faster than [¹⁸F]FMISO, uptake in hypoxic tumors was slower. The average tumor to muscle ratio at 2h post injection in large, hypoxic tumors with a volume greater than 686 mm³ was 1.7, which was similar to the observed ratio of 1.75 for [¹⁸F]FMISO. Although the new tracer showed improved pharmacokinetics when compared with the previously synthesised sulfoxides, further modifications to the chemical structure need to be made in order to offer significant in vivo imaging advantages over [¹⁸F]FMISO.
Gov't Doc #: 24767600
DOI: 10.1016/j.nucmedbio.2014.03.001
Type: Journal Article
Subjects: Click chemistry
Radiotracer metabolism
SK-RC-52 tumor model
Cell Hypoxia
Cell Line, Tumor
Hydrophobic and Hydrophilic Interactions
Isotope Labeling
Kidney Neoplasms.pathology
Positron-Emission Tomography.methods
Sulfoxides.chemistry.diagnostic use.pharmacokinetics
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