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Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model

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Abstract

Purpose

As primary osseous metastasis is the main adverse prognostic factor in patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour metastases has been established to examine the mechanisms of metastasis. The aim of this study was to evaluate the feasibility of diagnostic molecular imaging by small animal PET in this mouse model.

Methods

Human Ewing tumour cells were transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v. injection (n=17). The animals (mean weight 23.2 g) were studied 2–7 weeks after transplantation using a submillimetre resolution animal PET scanner. To assess glucose utilisation and bone metabolism, mice were scanned after intravenous injection of 9.6 MBq (mean) 2-[18F]fluoro-2-deoxy-D-glucose (FDG) or 9.4 MBq (mean) [18F]fluoride. Whole-body PET images were analysed visually and semi-quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological uptake were identified with respect to the physiological organ uptake in corresponding regions.

Results

Subcutaneously transplanted Ewing tumours demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT 2.2). After i.v. transplantation, the pattern of metastasis was similar to that in patients with metastases in lung, bone and soft tissue. These metastases showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous metastases were additionally visible on [18F]fluoride PET by virtue of decreased [18F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically.

Conclusion

Diagnostic molecular imaging of Ewing tumours and their small metastases in an in vivo NOD/scid mouse model is feasible using a submillimetre resolution PET scanner.

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Acknowledgements

The authors gratefully acknowledge the technicians Christine Bätza and Christiane Schäfers for their technical help with the PET imaging and semi-quantitative analysis and Sabine Schneeloch and Claire Feldhoff for their technical help with the histological and immunohistological examinations. The authors thank Dr. rer. nat. Klaus Kopka and Dr. rer. nat. Stefan Wagner for the production of the radiopharmaceuticals. Furthermore, they are grateful to Marilyn Law, PhD, for reviewing the manuscript with respect to the English language. This work was supported by the Innovative Medizinische Forschung (IMF) grant (FR 210321) from the University Hospital Münster, Germany.

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Author notes

  1. Josef Vormoor

    Present address: Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle, Great Britain

Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Strasse 33, 48149, Münster, Germany

    Christiane Franzius, Sven Hermann, Klaus Schäfers, Otmar Schober & Michael Schäfers

  2. Department of Pediatric Hematology and Oncology, University Hospital Münster, Münster, Germany

    Marc Hotfilder, Heribert Jürgens & Josef Vormoor

  3. Institute of Pathology, Heinrich-Heine-University, Düsseldorf, Germany

    Christopher Poremba & Helmut Erich Gabbert

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  1. Christiane Franzius
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Correspondence to Christiane Franzius.

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Franzius, C., Hotfilder, M., Poremba, C. et al. Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model. Eur J Nucl Med Mol Imaging 33, 1432–1441 (2006). https://doi.org/10.1007/s00259-006-0106-6

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  • DOI: https://doi.org/10.1007/s00259-006-0106-6

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