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An Evaluation of 2-deoxy-2-[18F]Fluoro-D-Glucose and 3′-deoxy-3′-[18F]-Fluorothymidine Uptake in Human Tumor Xenograft Models

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Abstract

Purpose

The aim of this study is to assess the variability of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]-FDG) and 3′-deoxy-3′-[18F]-fluorothymidine ([18F]-FLT) uptake in pre-clinical tumor models and examine the relationship between imaging data and related histological biomarkers.

Procedures

[18F]-FDG and [18F]-FLT studies were carried out in nine human tumor xenograft models in mice. A selection of the models underwent histological analysis for endpoints relevant to radiotracer uptake. Comparisons were made between in vitro uptake, in vivo imaging, and ex vivo histopathology data using quantitative and semi-quantitative analysis.

Results

In vitro data revealed that [1-14C]-2-deoxy-d-glucose ([14C]-2DG) uptake in the tumor cell lines was variable. In vivo, [18F]-FDG and [18F]-FLT uptake was highly variable across tumor types and uptake of one tracer was not predictive for the other. [14C]-2DG uptake in vitro did not predict for [18F]-FDG uptake in vivo. [18F]-FDG SUV was inversely proportional to Ki67 and necrosis levels and positively correlated with HKI. [18F]-FLT uptake positively correlated with Ki67 and TK1.

Conclusion

When evaluating imaging biomarkers in response to therapy, the choice of tumor model should take into account in vivo baseline radiotracer uptake, which can vary significantly between models.

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Acknowledgements

We thank the Radiopharmacy of the University Hospital of Tübingen for providing the radiotracers. We also thank John Foster, Alison Bigley, and Neil Gray of AstraZeneca for providing immunohistochemistry support.

Conflict of Interest

All work performed was funded by AstraZeneca. However, since no AstraZeneca product was evaluated in this study, this does not create any conflict of interest. Bernd Pichler has consulted for AstraZeneca, BayerHealthcare, Boehringer-Ingelheim, and Siemens Healthcare in the last 3 years. All other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. PHB Imaging Group, AstraZeneca, 19F22 Mereside, Alderley Park, Macclesfield, SK10 4TG, UK

    Heather Keen, Juliana Bales, Neill Gingles & Sally-Ann Ricketts

  2. Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany

    Bernd Pichler & Damaris Kukuk

  3. Oncodesign, Dijon, France

    Olivier Duchamp & Olivier Raguin

  4. Department of Experimental Oncology, University of Manchester, Manchester, UK

    Aoife Shannon

  5. Oncology iMed, R&D, AstraZeneca, Alderley Park, Macclesfield, UK

    Nichola Whalley, Vivien Jacobs & Stephen R. Wedge

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  1. Heather Keen
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Correspondence to Heather Keen.

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Ethics Statement

Animal experiments were performed according to the European ethical guidelines of animal experimentation, and in compliance with and the United Kingdom Co-ordinating Committee on Cancer Research guidelines [53]. The animal care unit at Oncodesign is authorized by the French ministries of Agriculture and Research (Agreement No. A21231011). All procedures with animals carried out at Oncodesign and the University of Tübingen were approved by the Animal Care and Use Committee of Pharmacy and Medicine University (Dijon) and were submitted to the ethical committee of the University of Tübingen (Tübingen, Germany). Alderley Park studies were carried out in accordance with the UK Home Office Animals (Scientific Procedures) Act 1986.

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Keen, H., Pichler, B., Kukuk, D. et al. An Evaluation of 2-deoxy-2-[18F]Fluoro-D-Glucose and 3′-deoxy-3′-[18F]-Fluorothymidine Uptake in Human Tumor Xenograft Models. Mol Imaging Biol 14, 355–365 (2012). https://doi.org/10.1007/s11307-011-0504-4

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