title: The flow-metabolic phenotype of primary colorectal cancer: assessment by integrated 18F-FDG PET/perfusion CT with histopathologic correlation.
abstract: The aim of this study was to assess the in vivo flow-metabolic phenotype in primary colorectal cancer with integrated (18)F-FDG PET/perfusion CT and its relationship to gold standard histopathologic assessment of angiogenesis and hypoxia.
  
  
  METHODS
  45 patients (26 male and 19 female; mean age, 67.6 y) with primary colorectal cancer underwent integrated (18)F-FDG PET/perfusion CT, deriving tumor glucose metabolism (maximum standardized uptake value) and regional blood flow. From this cohort, 35 underwent surgery subsequently, without intervening neoadjuvant treatment, allowing histopathologic correlation with tumor stage, CD105 microvessel density, vascular endothelial growth factor (VEGF), glucose transporter protein 1 (Glut-1), and hypoxia-inducible factor 1 expression.
  
  
  RESULTS
  The flow-metabolic ratio was significantly lower for tumors with higher VEGF (3.65 vs. 5.98; P = 0.01) or hypoxia-inducible factor 1 expression (3.63 vs. 5.48; P = 0.04) versus tumors with lower expression. There were significant negative correlations between the tumor flow-metabolic ratio and VEGF expression (r = -0.55, P = 0.0008), indicating that tumors with low blood flow but higher metabolism were associated with higher VEGF expression. Flow and metabolism were coupled in higher-stage (stage III/IV) tumors but not lower-stage tumors (stage I/II) (r = 0.47, P = 0.03, vs. r = 0.09, P = 0.65, respectively.
  
  
  CONCLUSIONS
  Tumors with a low-flow-high-metabolism phenotype demonstrated higher VEGF expression and may reflect a more angiogenic phenotype.
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom. vicky.goh@kcl.ac.uk
authors.forename: Vicky
authors.initials: V
authors.lastname: Goh
authors.forename: Alec
authors.initials: A
authors.lastname: Engledow
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Justo
authors.forename: Manu
authors.initials: M
authors.lastname: Shastry
authors.forename: Jacquie
authors.initials: J
authors.lastname: Peck
authors.forename: Glen
authors.initials: G
authors.lastname: Blackman
authors.forename: Raymondo
authors.initials: R
authors.lastname: Endozo
authors.forename: Stuart
authors.initials: S
authors.lastname: Taylor
authors.forename: Steve
authors.initials: S
authors.lastname: Halligan
authors.forename: Peter
authors.initials: P
authors.lastname: Ell
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Groves
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015687:Cell Hypoxia; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000473:pathology; D055420:Perfusion Imaging; D010641:Phenotype; D049268:Positron-Emission Tomography; D012039:Regional Blood Flow; D014057:Tomography, X-Ray Computed
chemical_list: D019788:Fluorodeoxyglucose F18