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Applying Advanced Imaging Techniques to a Murine Model of Orthotopic Osteosarcoma.

Broadhead ML, Lokmic Z, Tan ML, Stevenson A, Binns DS, Cullinane C, Hicks RJ, Choong PF, Myers DE - Front Surg (2015)

Bottom Line: Treatment agent [pigment epithelium-derived factor (PEDF)] was delivered to the peritoneal cavity.Primary tumors and metastases were evaluated by in vivo bioluminescent assays, micro-computed tomography, [(18)F]-Fluoride-PET and [(18)F]-FDG-PET. [(18)F]-Fluoride-PET was more sensitive than [(18)F]-FDG-PET for detecting early disease.Both [(18)F]-Fluoride-PET and [(18)F]-FDG-PET showed progressive disease in the model, with fourfold and twofold increases in standardized uptake value (p < 0.05) by the study endpoint, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, St. Vincent's Hospital Melbourne, University of Melbourne , Fitzroy, VIC , Australia.

ABSTRACT

Introduction: Reliable animal models are required to evaluate novel treatments for osteosarcoma. In this study, the aim was to implement advanced imaging techniques in a murine model of orthotopic osteosarcoma to improve disease modeling and the assessment of primary and metastatic disease.

Materials and methods: Intra-tibial injection of luciferase-tagged OPGR80 murine osteosarcoma cells was performed in Balb/c nude mice. Treatment agent [pigment epithelium-derived factor (PEDF)] was delivered to the peritoneal cavity. Primary tumors and metastases were evaluated by in vivo bioluminescent assays, micro-computed tomography, [(18)F]-Fluoride-PET and [(18)F]-FDG-PET.

Results: [(18)F]-Fluoride-PET was more sensitive than [(18)F]-FDG-PET for detecting early disease. Both [(18)F]-Fluoride-PET and [(18)F]-FDG-PET showed progressive disease in the model, with fourfold and twofold increases in standardized uptake value (p < 0.05) by the study endpoint, respectively. In vivo bioluminescent assay showed that systemically delivered PEDF inhibited growth of primary osteosarcoma.

Discussion: Application of [(18)F]-Fluoride-PET and [(18)F]-FDG-PET to an established murine model of orthotopic osteosarcoma has improved the assessment of disease. The use of targeted imaging should prove beneficial for the evaluation of new approaches to osteosarcoma therapy.

No MeSH data available.


Related in: MedlinePlus

(A) Positron-emission tomography parameters obtained 1 week following intra-tibial injection and at the study endpoint (SUV, standardized uptake value; TBR, tumor to background ratio; MTV, metabolic tumor volume; *p < 0.05). [18F]-Fluoride SUV was the most sensitive parameter for detecting early stage disease. Between week 1 and the study endpoint, the sevenfold increase in [18F]-Fluoride % ID was the greatest, making it the most sensitive marker of disease progression. (B) [18F]-Fluoride and [18F]-FDG-PET imaging were performed at the end of week 1 and the study endpoint. Images show increased uptake of the PET tracer in the left hind limb of the mouse. Pulmonary metastatic disease was not detectable on PET imaging.
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Figure 4: (A) Positron-emission tomography parameters obtained 1 week following intra-tibial injection and at the study endpoint (SUV, standardized uptake value; TBR, tumor to background ratio; MTV, metabolic tumor volume; *p < 0.05). [18F]-Fluoride SUV was the most sensitive parameter for detecting early stage disease. Between week 1 and the study endpoint, the sevenfold increase in [18F]-Fluoride % ID was the greatest, making it the most sensitive marker of disease progression. (B) [18F]-Fluoride and [18F]-FDG-PET imaging were performed at the end of week 1 and the study endpoint. Images show increased uptake of the PET tracer in the left hind limb of the mouse. Pulmonary metastatic disease was not detectable on PET imaging.

Mentions: Imaging with [18F]-Fluoride and [18F]-FDG were performed on sequential days, at days 8 and 9 of the study and at days 32 and 33. Maximum standardized uptake value (SUV), TBR, percentage of injected dose (% ID), and MTV were calculated. [18F]-Fluoride SUV was the most sensitive parameter for detecting early stage disease in the OPGR80 orthotopic osteosarcoma model, with an average [18F]-Fluoride SUV reading of 4.723, 1 week after intra-tibial injection. Taking arbitrary cut-offs of 2.0 and 3.0 for SUV and TBR, respectively, other readings obtained at week 1 were not of sufficient magnitude to indicate malignancy (Figures 4A,B).


Applying Advanced Imaging Techniques to a Murine Model of Orthotopic Osteosarcoma.

Broadhead ML, Lokmic Z, Tan ML, Stevenson A, Binns DS, Cullinane C, Hicks RJ, Choong PF, Myers DE - Front Surg (2015)

(A) Positron-emission tomography parameters obtained 1 week following intra-tibial injection and at the study endpoint (SUV, standardized uptake value; TBR, tumor to background ratio; MTV, metabolic tumor volume; *p < 0.05). [18F]-Fluoride SUV was the most sensitive parameter for detecting early stage disease. Between week 1 and the study endpoint, the sevenfold increase in [18F]-Fluoride % ID was the greatest, making it the most sensitive marker of disease progression. (B) [18F]-Fluoride and [18F]-FDG-PET imaging were performed at the end of week 1 and the study endpoint. Images show increased uptake of the PET tracer in the left hind limb of the mouse. Pulmonary metastatic disease was not detectable on PET imaging.
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Related In: Results  -  Collection

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Figure 4: (A) Positron-emission tomography parameters obtained 1 week following intra-tibial injection and at the study endpoint (SUV, standardized uptake value; TBR, tumor to background ratio; MTV, metabolic tumor volume; *p < 0.05). [18F]-Fluoride SUV was the most sensitive parameter for detecting early stage disease. Between week 1 and the study endpoint, the sevenfold increase in [18F]-Fluoride % ID was the greatest, making it the most sensitive marker of disease progression. (B) [18F]-Fluoride and [18F]-FDG-PET imaging were performed at the end of week 1 and the study endpoint. Images show increased uptake of the PET tracer in the left hind limb of the mouse. Pulmonary metastatic disease was not detectable on PET imaging.
Mentions: Imaging with [18F]-Fluoride and [18F]-FDG were performed on sequential days, at days 8 and 9 of the study and at days 32 and 33. Maximum standardized uptake value (SUV), TBR, percentage of injected dose (% ID), and MTV were calculated. [18F]-Fluoride SUV was the most sensitive parameter for detecting early stage disease in the OPGR80 orthotopic osteosarcoma model, with an average [18F]-Fluoride SUV reading of 4.723, 1 week after intra-tibial injection. Taking arbitrary cut-offs of 2.0 and 3.0 for SUV and TBR, respectively, other readings obtained at week 1 were not of sufficient magnitude to indicate malignancy (Figures 4A,B).

Bottom Line: Treatment agent [pigment epithelium-derived factor (PEDF)] was delivered to the peritoneal cavity.Primary tumors and metastases were evaluated by in vivo bioluminescent assays, micro-computed tomography, [(18)F]-Fluoride-PET and [(18)F]-FDG-PET. [(18)F]-Fluoride-PET was more sensitive than [(18)F]-FDG-PET for detecting early disease.Both [(18)F]-Fluoride-PET and [(18)F]-FDG-PET showed progressive disease in the model, with fourfold and twofold increases in standardized uptake value (p < 0.05) by the study endpoint, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, St. Vincent's Hospital Melbourne, University of Melbourne , Fitzroy, VIC , Australia.

ABSTRACT

Introduction: Reliable animal models are required to evaluate novel treatments for osteosarcoma. In this study, the aim was to implement advanced imaging techniques in a murine model of orthotopic osteosarcoma to improve disease modeling and the assessment of primary and metastatic disease.

Materials and methods: Intra-tibial injection of luciferase-tagged OPGR80 murine osteosarcoma cells was performed in Balb/c nude mice. Treatment agent [pigment epithelium-derived factor (PEDF)] was delivered to the peritoneal cavity. Primary tumors and metastases were evaluated by in vivo bioluminescent assays, micro-computed tomography, [(18)F]-Fluoride-PET and [(18)F]-FDG-PET.

Results: [(18)F]-Fluoride-PET was more sensitive than [(18)F]-FDG-PET for detecting early disease. Both [(18)F]-Fluoride-PET and [(18)F]-FDG-PET showed progressive disease in the model, with fourfold and twofold increases in standardized uptake value (p < 0.05) by the study endpoint, respectively. In vivo bioluminescent assay showed that systemically delivered PEDF inhibited growth of primary osteosarcoma.

Discussion: Application of [(18)F]-Fluoride-PET and [(18)F]-FDG-PET to an established murine model of orthotopic osteosarcoma has improved the assessment of disease. The use of targeted imaging should prove beneficial for the evaluation of new approaches to osteosarcoma therapy.

No MeSH data available.


Related in: MedlinePlus