TY - JOUR
T1 - Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model
AU - Franzius, Christiane
AU - Hotfilder, Marc
AU - Poremba, Christopher
AU - Hermann, Sven
AU - Schäfers, Klaus
AU - Gabbert, Helmut Erich
AU - Jürgens, Heribert
AU - Schober, Otmar
AU - Schäfers, Michael
AU - Vormoor, Josef
N1 - Funding Information:
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.
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
KW - [F]fluoride
KW - Ewing tumours
KW - FDG
KW - Mouse model
KW - Small animal PET
UR - http://www.scopus.com/inward/record.url?scp=33845368332&partnerID=8YFLogxK
U2 - 10.1007/s00259-006-0106-6
DO - 10.1007/s00259-006-0106-6
M3 - Article
C2 - 16896672
AN - SCOPUS:33845368332
SN - 1619-7070
VL - 33
SP - 1432
EP - 1441
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 12
ER -