title: Molecular mechanism underlying the detection of colorectal cancer by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography.
abstract: BACKGROUND
  Biological imaging by positron emission tomography (PET) using 18F-2-fluoro-2-deoxy-D-glucose (FDG) has been widely used clinically for the detection of primary tumors and for early prediction of response to chemotherapy. In this study, we examined the molecular mechanism underlying the detection of colorectal cancers by FDG-PET.
  
  
  METHODS
  In all, 37 patients with colorectal cancer were examined with FDG-PET, and the maximal standardized uptake value (SUV) was calculated. Using surgical tissue samples, we examined the expression levels of hypoxia-inducible factor alpha (HIF1α), a marker of tissue hypoxia; proliferative cellular nuclear antigen (PCNA), a marker of proliferation; and glucose transporter (GLUT)1 and hexokinase (HK)2, protein of glucose uptake by using reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  All except two colorectal cancer lesions showed increased uptake of FDG. The mean SUV of FDG-PET was 12.0 ± 1.2 (±SEM). The mean mRNA expression levels of GLUT1 and HK2 were significantly higher in cancer tissues than in the surrounding normal mucosa. Moreover, to promote the upregulation of glucose uptake, the expressions of HIF1α and PCNA were induced to 2.6 and 3.3 times higher than that in the normal mucosa. However, the quantitative correlation analysis showed SUV was correlated with HIF1α expression but not with PCNA expression.
  
  
  CONCLUSIONS
  Our molecular-based analysis suggested that FDG accumulation due to induction of glucose uptake proteins might be associated with the hypoxic environment in tumors rather than the tumor growth. Therefore, for assessing the efficacy of chemotherapy using FDG-PET, we must keep in mind that SUV does not indicate the tumor growth directly.
authors: Department of Gastroenterological Surgery, Kagawa University, 1750-11, Ikenobe, Miki, Kita, Takamatsu, Kagawa, 761-0793, Japan. izuishi@kms.ac.jp
authors: Kunihiko
authors: K
authors: Izuishi
authors: Yuka
authors: Y
authors: Yamamoto
authors: Takanori
authors: T
authors: Sano
authors: Ryusuke
authors: R
authors: Takebayashi
authors: Yoshihiro
authors: Y
authors: Nishiyama
authors: Hirohito
authors: H
authors: Mori
authors: Tsutomu
authors: T
authors: Masaki
authors: Asahiro
authors: A
authors: Morishita
authors: Yasuyuki
authors: Y
authors: Suzuki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D049268:Positron-Emission Tomography; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018809:Proliferating Cell Nuclear Antigen; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D006593:Hexokinase; D005947:Glucose