title: Quantitative assessment of heterogeneity in tumor metabolism using FDG-PET.
abstract: OBJECTIVE
  [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) images are usually quantitatively analyzed in "whole-tumor" volumes of interest. Also parameters determined with dynamic PET acquisitions, such as the Patlak glucose metabolic rate (MR(glc)) and pharmacokinetic rate constants of two-tissue compartment modeling, are most often derived per lesion. We propose segmentation of tumors to determine tumor heterogeneity, potentially useful for dose-painting in radiotherapy and elucidating mechanisms of FDG uptake.
  
  
  METHODS
  In 41 patients with 104 lesions, dynamic FDG-PET was performed. On MR(glc) images, tumors were segmented in quartiles of background subtracted maximum MR(glc) (0%-25%, 25%-50%, 50%-75%, and 75%-100%). Pharmacokinetic analysis was performed using an irreversible two-tissue compartment model in the three segments with highest MR(glc) to determine the rate constants of FDG metabolism.
  
  
  RESULTS
  From the highest to the lowest quartile, significant decreases of uptake (K(1)), washout (k(2)), and phosphorylation (k(3)) rate constants were seen with significant increases in tissue blood volume fraction (V(b)).
  
  
  CONCLUSIONS
  Tumor regions with highest MR(glc) are characterized by high cellular uptake and phosphorylation rate constants with relatively low blood volume fractions. In regions with less metabolic activity, the blood volume fraction increases and cellular uptake, washout, and phosphorylation rate constants decrease. These results support the hypothesis that regional tumor glucose phosphorylation rate is not dependent on the transport of nutrients (i.e., FDG) to the tumor.
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. d.vriens@nucmed.umcn.nl
authors.forename: Dennis
authors.initials: D
authors.lastname: Vriens
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Disselhorst
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Lioe-Fee
authors.initials: LF
authors.lastname: de Geus-Oei
authors.forename: Eric P
authors.initials: EP
authors.lastname: Visser
mesh_terms: D000328:Adult; D000368:Aged; D001810:Blood Volume; D001943:Breast Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D010766:Phosphorylation; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose