Abstract
Purpose
2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide labeled with [18F]-fluorine ([18F]EF5), a promising tracer for tumor hypoxia, has previously been synthesized in low yields and low specific radioactivity. In pharmacokinetic evaluations, in the presence of non-radioactive EF5, a uniform and low background uptake and high in vivo stability of [18F]EF5 have been demonstrated. Our purpose was to increase the specific radioactivity of [18F]EF5 to enable to study the pharmacokinetics at trace level.
Procedures
[18F]EF5 was synthesized using high specific radioactivity electrophilic [18F]F2 as labelling reagent. Biodistribution of [18F]EF5 was determined in a prostate tumor mouse model, and formation of radiolabelled metabolites was studied in mouse, rat and human plasma.
Results
On average, 595 ± 153 MBq of [18F]EF5 was produced. Specific radioactivity was 6.6 ± 1.9 GBq/μmol and the radiochemical purity exceeded 99.0%. [18F]EF5 was distributed uniformly in tissues, with highest uptake in liver, kidney, and intestine. Several radiolabelled metabolites were detected in mouse plasma and tissues, whereas low amounts of metabolites were detected in human and rat plasma.
Conclusions
[18F]EF5 was synthesized by electrophilic labelling with high quality and high yields. Pharmacokinetics of [18F]EF5 was determined at trace level in several species. Our results suggest that the trace-level approach does not affect the biodistribution of [18F]EF5. Extensive metabolism was seen in mouse.
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Acknowledgements
This work was supported in part by the European Union's FP6 Commission “Biocare” (Molecular Imaging for Biologically Optimized Cancer Therapy) under the contract number 505785. Additional funding was obtained from The Finnish Cancer Organizations, Foundation for the Finnish Cancer Institute, the Hospital District of Southwest Finland's EVO-foundation, and the Academy of Finland (grant number 116084).The authors wish to thank Professor Cameron Koch (Radiation Oncology Department, School of Medicine, University of Pennsylvania, Philadelphia, USA) and the US National Cancer Institute for providing EF5 and its precursor free of charge.
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The authors declare that they have no conflict of interest.
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Eskola, O., Grönroos, T.J., Forsback, S. et al. Tracer Level Electrophilic Synthesis and Pharmacokinetics of the Hypoxia Tracer [18F]EF5. Mol Imaging Biol 14, 205–212 (2012). https://doi.org/10.1007/s11307-011-0484-4
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DOI: https://doi.org/10.1007/s11307-011-0484-4