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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 (pā€‰<ā€‰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

Histological assessment. (A) Hematoxylin and eosin (H&E) stained section of undifferentiated primary tumor (t). Tumor cells (arrows) are observed infiltrating the adjacent skeletal muscle (m); (B) Immunohistochemistry for CD31 showing positively stained endothelium (arrows), within both muscle and tumor; (C) Immunohistochemistry for VEGF-1 showing positively stained cells within the peripheral region of the tumor (arrows); (D) H&E stained section of tumor and adjacent skeletal muscle (m). The tumor consists of a highly cellular peripheral zone (p) and a matrix-producing central zone (c); (E) Alizarin Red S stained tumor identifying the presence of deposited calcium as dark red precipitate (arrow) within the central zone; (F) Alizarin Red S stained tumor under polarized light confirms the presence of calcium within tissue evident here as bright red precipitate; (G) H&E stained lung tissue (l) with metastatic lesion (contained within solid line). The metastasis possesses a matrix-producing central zone (c); (H) Alizarin Red S stained section showing the presence of calcium as dark red precipitate in the central zone (arrow); (I) Alizarin Red S stained lung tissue under polarized light. Calcified regions are evident as bright red precipitate.
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Figure 7: Histological assessment. (A) Hematoxylin and eosin (H&E) stained section of undifferentiated primary tumor (t). Tumor cells (arrows) are observed infiltrating the adjacent skeletal muscle (m); (B) Immunohistochemistry for CD31 showing positively stained endothelium (arrows), within both muscle and tumor; (C) Immunohistochemistry for VEGF-1 showing positively stained cells within the peripheral region of the tumor (arrows); (D) H&E stained section of tumor and adjacent skeletal muscle (m). The tumor consists of a highly cellular peripheral zone (p) and a matrix-producing central zone (c); (E) Alizarin Red S stained tumor identifying the presence of deposited calcium as dark red precipitate (arrow) within the central zone; (F) Alizarin Red S stained tumor under polarized light confirms the presence of calcium within tissue evident here as bright red precipitate; (G) H&E stained lung tissue (l) with metastatic lesion (contained within solid line). The metastasis possesses a matrix-producing central zone (c); (H) Alizarin Red S stained section showing the presence of calcium as dark red precipitate in the central zone (arrow); (I) Alizarin Red S stained lung tissue under polarized light. Calcified regions are evident as bright red precipitate.

Mentions: Hematoxylin and eosin stained sections demonstrated tumor tissue consisting of pleomorphic spindle-shaped cells producing an eosinophilic matrix. Variable degrees of tumor differentiation were seen both within individual samples and across treatment groups. Some tumors consisted solely of pleomorphic spindle cells, while others showed a peripheral zone of invading malignant cells surrounding a central zone of increased matrix production. All sections showed cells at the margin of the tumors were observed infiltrating between striated skeletal muscles. Cells were also observed invading neurovascular structures (Figure 7A). No distinct tumor morphological patterns have been observed between the treatment groups.


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)

Histological assessment. (A) Hematoxylin and eosin (H&E) stained section of undifferentiated primary tumor (t). Tumor cells (arrows) are observed infiltrating the adjacent skeletal muscle (m); (B) Immunohistochemistry for CD31 showing positively stained endothelium (arrows), within both muscle and tumor; (C) Immunohistochemistry for VEGF-1 showing positively stained cells within the peripheral region of the tumor (arrows); (D) H&E stained section of tumor and adjacent skeletal muscle (m). The tumor consists of a highly cellular peripheral zone (p) and a matrix-producing central zone (c); (E) Alizarin Red S stained tumor identifying the presence of deposited calcium as dark red precipitate (arrow) within the central zone; (F) Alizarin Red S stained tumor under polarized light confirms the presence of calcium within tissue evident here as bright red precipitate; (G) H&E stained lung tissue (l) with metastatic lesion (contained within solid line). The metastasis possesses a matrix-producing central zone (c); (H) Alizarin Red S stained section showing the presence of calcium as dark red precipitate in the central zone (arrow); (I) Alizarin Red S stained lung tissue under polarized light. Calcified regions are evident as bright red precipitate.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 7: Histological assessment. (A) Hematoxylin and eosin (H&E) stained section of undifferentiated primary tumor (t). Tumor cells (arrows) are observed infiltrating the adjacent skeletal muscle (m); (B) Immunohistochemistry for CD31 showing positively stained endothelium (arrows), within both muscle and tumor; (C) Immunohistochemistry for VEGF-1 showing positively stained cells within the peripheral region of the tumor (arrows); (D) H&E stained section of tumor and adjacent skeletal muscle (m). The tumor consists of a highly cellular peripheral zone (p) and a matrix-producing central zone (c); (E) Alizarin Red S stained tumor identifying the presence of deposited calcium as dark red precipitate (arrow) within the central zone; (F) Alizarin Red S stained tumor under polarized light confirms the presence of calcium within tissue evident here as bright red precipitate; (G) H&E stained lung tissue (l) with metastatic lesion (contained within solid line). The metastasis possesses a matrix-producing central zone (c); (H) Alizarin Red S stained section showing the presence of calcium as dark red precipitate in the central zone (arrow); (I) Alizarin Red S stained lung tissue under polarized light. Calcified regions are evident as bright red precipitate.
Mentions: Hematoxylin and eosin stained sections demonstrated tumor tissue consisting of pleomorphic spindle-shaped cells producing an eosinophilic matrix. Variable degrees of tumor differentiation were seen both within individual samples and across treatment groups. Some tumors consisted solely of pleomorphic spindle cells, while others showed a peripheral zone of invading malignant cells surrounding a central zone of increased matrix production. All sections showed cells at the margin of the tumors were observed infiltrating between striated skeletal muscles. Cells were also observed invading neurovascular structures (Figure 7A). No distinct tumor morphological patterns have been observed between the treatment groups.

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 (pā€‰<ā€‰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