title: Biological correlation of ¹⁸F-FDG uptake on PET in pulmonary neuroendocrine tumors.
abstract: BACKGROUND
  It is widely recognized that pulmonary neuroendocrine tumors (PNET) include a spectrum that ranges from low-grade typical carcinoid (TC) and atypical carcinoid (AC) to high-grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). However, little is known about the usefulness of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron-emission tomography (PET) in such tumors. We therefore, conducted a study including the analysis of the underlying biology of (18)F-FDG uptake.
  
  
  METHODS
  Thirty-four patients with early-stage PNETs who underwent (18)F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut1 and Glut3), hypoxia-inducible factor-1 alpha (HIF-1α), hexokinase-I, vascular endothelial growth factor (VEGF), microvessel density (MVD) determined by CD34 and (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.
  
  
  RESULTS
  (18)F-FDG uptake correlated significantly with Glut1, HIF-1α, VEGF and CD34 expression. Uptake of (18)F-FDG tended to increase from low-grade to high-grade PNETs. Tumor metabolic activity was a useful marker for predicting postoperative prognosis in patients with early-stage PNETs.
  
  
  CONCLUSIONS
  The amount of (18)F-FDG uptake is determined by the presence of glucose metabolism, hypoxia and angiogenesis.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, Shizuoka, 411-8777, Japan. kkaira1970@yahoo.co.jp.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kondo
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019275:Radiopharmaceuticals; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG PET; GLUT1; angiogenesis; glucose metabolism; hypoxia; pulmonary neuroendocrine tumor