Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model.
OBJECTIVE
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-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) or 9.4 MBq (mean) [(18)F]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 [(18)F]fluoride PET by virtue of decreased [(18)F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically.


CONCLUSIONS
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.
Franzius
Christiane
C
Department of Nuclear Medicine, University Hospital Münster, Münster, Germany. franziu@uni-muenster.de
Hotfilder
Marc
M
Poremba
Christopher
C
Hermann
Sven
S
Schäfers
Klaus
K
Gabbert
Helmut Erich
HE
Jürgens
Heribert
H
Schober
Otmar
O
Schäfers
Michael
M
Vormoor
Josef
J
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005459:Fluorides / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D012512:Sarcoma, Ewing / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D013194:Staining and Labeling; D014183:Transplantation, Heterologous
D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005459:Fluorides