Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model
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.
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.
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.
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.
KeywordsSmall animal PET FDG [18F]fluoride Ewing tumours Mouse model
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.
- 10.Vormoor J, Decker S, Hotfilder M, Poremba C, Dockhorn-Dwornizcak B, Jürgens H. Mechanisms of Ewing tumor cell metastasis to the bone marrow. Blood 2000;96:153bGoogle Scholar
- 16.Wieland BW, Bida GT, Padgett HC, Go H. Current status of CTI target systems for the production of PET radiochemicals. Proceedings of the 3rd Workshop on Targetry and Target Chemistry, Vancouver, British Columbia, Canada, 19–23 June 1989Google Scholar
- 25.Boisgard R, Vincent-Naulleau S, Leplat J-J, Bouet S, Le Chalony C, Tricaud Y, et al. A new animal model for the imaging of melanoma: correlation of FDG PET with clinical outcome, macroscopic aspects and histological classification in melanoblastoma-bearing Libechav minipigs. Eur J Nucl Med Mol Imaging 2003;30:826–834PubMedCrossRefGoogle Scholar