Alexandr Kristian1, Line B Nilsen2, Kathrine Røe2, Mona-Elisabeth Revheim3, Olav Engebråten4, Gunhild M Mælandsmo5, Ruth Holm6, Eirik Malinen7, Therese Seierstad8. 1. Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway. 2. Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway. 3. Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway ; Department of Radiology and Nuclear Medicine, Oslo University Hospital, 0424 Oslo, Norway. 4. Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway ; Department of Oncology, Oslo University Hospital, 0424 Oslo, Norway. 5. Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway ; Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, Norway. 6. Department of Pathology, Oslo University Hospital, 0424 Oslo, Norway. 7. Department of Medical Physics, Oslo University Hospital, 0424 Oslo, Norway ; Department of Physics, University of Oslo, 0316 Oslo, Norway. 8. Department of Radiology and Nuclear Medicine, Oslo University Hospital, 0424 Oslo, Norway ; Department of Health Sciences, Buskerud University College, 3007 Drammen, Norway.
Abstract
PURPOSE: To compare dynamic 2-deoxy-2-[(18) F]fluoro-D-glucose positron emission tomography ((18) F-FDG PET) parameters in two selected human breast cancer xenografts and to evaluate associations with immunohistochemistry and histology. PROCEDURES: Dynamic (18) F-FDG PET of luminal-like MAS98.06 and basal-like MAS98.12 xenografts was performed, and the compartmental transfer rates (k 1 ,k 2 ,k 3 ), blood volume fraction (v B ) and metabolic rate of (18) F-FDG(MR FDG ) were estimated from pharmacokinetic model analysis. After sacrifice, analyses of hypoxia (pimonidazole), proliferation (Ki-67), vascularization (CD31), glucose transport receptor (GLUT1) and necrosis (HE) was performed. The level of hexokinase 2 (HK2) was estimated from Western blot analysis. RESULTS: The (18) F-FDG uptake curves for the two xenografts were significantly different (p < 0.05). k 1 and v B were higher for MAS98.12 (p < 0.01), while k 3 was higher for MAS98.06 (p < 0.01). MAS98.12 had a higher fraction of stromal tissue and higher microvessel density (MVD), and it was less necrotic and hypoxic than MAS98.06. MAS98.12 had stronger positive GLUT1 staining and lower Ki-67 than MAS98.06. In both models significant correlations were found between k 1 and the GLUT1 score, between k 3 and the level of HK2, and between v B and MVD. CONCLUSIONS: Significant differences in dynamic (18) F-FDG parameters between the two human breast cancer xenografts were found. The differences could be explained by underlying histological and physiological characteristics.
PURPOSE: To compare dynamic 2-deoxy-2-[(18) F]fluoro-D-glucose positron emission tomography ((18) F-FDG PET) parameters in two selected humanbreast cancer xenografts and to evaluate associations with immunohistochemistry and histology. PROCEDURES: Dynamic (18) F-FDG PET of luminal-like MAS98.06 and basal-like MAS98.12 xenografts was performed, and the compartmental transfer rates (k 1 ,k 2 ,k 3 ), blood volume fraction (v B ) and metabolic rate of (18) F-FDG(MR FDG ) were estimated from pharmacokinetic model analysis. After sacrifice, analyses of hypoxia (pimonidazole), proliferation (Ki-67), vascularization (CD31), glucose transport receptor (GLUT1) and necrosis (HE) was performed. The level of hexokinase 2 (HK2) was estimated from Western blot analysis. RESULTS: The (18) F-FDG uptake curves for the two xenografts were significantly different (p < 0.05). k 1 and v B were higher for MAS98.12 (p < 0.01), while k 3 was higher for MAS98.06 (p < 0.01). MAS98.12 had a higher fraction of stromal tissue and higher microvessel density (MVD), and it was less necrotic and hypoxic than MAS98.06. MAS98.12 had stronger positive GLUT1 staining and lower Ki-67 than MAS98.06. In both models significant correlations were found between k 1 and the GLUT1 score, between k 3 and the level of HK2, and between v B and MVD. CONCLUSIONS: Significant differences in dynamic (18) F-FDG parameters between the two humanbreast cancer xenografts were found. The differences could be explained by underlying histological and physiological characteristics.
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