title: Dynamic (18) F-FDG PET for Assessment of Tumor Physiology in Two Breast Carcinoma Xenografts.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Kristian
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway.
authors.forename: Line B
authors.initials: LB
authors.lastname: Nilsen
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway.
authors.forename: Kathrine
authors.initials: K
authors.lastname: Røe
authors.affiliation: Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway ; Department of Radiology and Nuclear Medicine, Oslo University Hospital, 0424 Oslo, Norway.
authors.forename: Mona-Elisabeth
authors.initials: ME
authors.lastname: Revheim
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway ; Department of Oncology, Oslo University Hospital, 0424 Oslo, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Engebråten
authors.affiliation: 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.
authors.forename: Gunhild M
authors.initials: GM
authors.lastname: Mælandsmo
authors.affiliation: Department of Pathology, Oslo University Hospital, 0424 Oslo, Norway.
authors.forename: Ruth
authors.initials: R
authors.lastname: Holm
authors.affiliation: Department of Medical Physics, Oslo University Hospital, 0424 Oslo, Norway ; Department of Physics, University of Oslo, 0316 Oslo, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Malinen
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital, 0424 Oslo, Norway ; Department of Health Sciences, Buskerud University College, 3007 Drammen, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
keywords: Breast carcinoma; Dynamic 18 F-FDG PET; GLUT1; Ki-67; Kinetic analysis; Perfusion