title: Dual-energy dynamic CT of lung adenocarcinoma: correlation of iodine uptake with tumor gene expression.
abstract: OBJECTIVE
  To compare iodine content (IC) of solitary lung cancer using dynamic measurements of CT attenuation (Hounsfield Units, HU) and to correlate their quantitative CT data with expressions of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and hypoxia-inducible factor-1α (HIF-1α) using immunostaining methods.
  
  
  METHODS
  This study included 18 patients with adenocarcinoma, who undergone dual energy dynamic multiphase CT to examine solitary lung nodules (6 part-solid and 12 solid nodules). Tumor size was 21.1 mm±8.1 (9-39mm) [Mean±SD (range)]. Contrast volume was determined by weight (2ml/kg). Contrast volume and injection rate were 110.5 ml±17.2 (80-144ml) and 1.84ml/s±0.30 (1.3-2.4ml/s), respectively. Enhancement values ([CT value at each delayed scan-CT value at unenhanced scan]) and net enhancement values ([peak CT value-CT value at unenhanced scan]) were calculated in HU from 65keV monochromatic image. IC at each delayed scan was measured in mg/cm(3) from the iodine-water material decomposition pair on the advantage workstation VolumeShare4. Immunostaining using VEGF, EGFR, and HIF-1α was performed by two pathologists, who evaluated the expression level of them subjectively. Statistical analyses were performed with rank correlation tests and regression analysis.
  
  
  RESULTS
  IC at 2- and 3-minute delayed scan (x) and immunostaining score of HIF-1α (y) showed a significantly positive correlation (r=0.64 and 0.52, p=0.004 and 0.03): regression equation, y=1.34+0.58x and y=1.51+0.55x, respectively.
  
  
  CONCLUSIONS
  Dual-energy dynamic multiphase CT can measure iodine content in lung adenocarcinoma. Iodine content at 2- and 3-minute delayed scan might correlate with the expression level of HIF-1α.
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka, 565-0871, Japan. Electronic address: m-yanagawa@radiol.med.osaka-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yanagawa
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka, 565-0871, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka, 565-0871, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hata
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka, 565-0871, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka, 565-0871, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Gyobu
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka, 565-0871, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka, 565-0871, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Honda
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka, 565-0871, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tomiyama
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D003287:Contrast Media / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007455:Iodine / Q000032:analysis / Q000493:pharmacokinetics*; D007472:Iohexol / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics; D011856:Radiographic Image Enhancement; D003074:Solitary Pulmonary Nodule / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods*; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D003287:Contrast Media; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007472:Iohexol; D007455:Iodine; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Dual-energy dynamic multiphase CT; Iodine content; hypoxia-inducible factor-1α; lung adenocarcinoma