title: 64Cu-ATSM Hypoxia Positron Emission Tomography for Detection of Conduit Ischemia in an Experimental Rat Esophagectomy Model.
abstract: BACKGROUND
  We designed a hypoxia-imaging modality to detect ischemia of the gastric conduit after esophagectomy.
  
  
  METHODS
  A rat esophagectomy model was created using 12-16-week-old, 300-350 g male Sprague-Dawley rats. In the operation group (n=6), partial gastric devascularization was performed by ligating the left gastric artery and the short gastric arteries and an esophagogastric anastomosis was performed. In the control group (n=6), the esophageal-gastric junction was incised and suturing was performed without gastric devascularization. Positron emission tomography (PET) images were taken using a microPET rodent model scanner, 24 h after the initial operation, after injection of 200 μCi 64Cu-diacetyl-bis (N4-methylsemicarbazone) (64Cu-ATSM) and pimonidazole 120 mg/kg. After microPET imaging, autoradiography and immunohistochemistry were performed.
  
  
  RESULTS
  The PET image revealed 64Cu-ATSM uptake at the fundus in the operation group 3 h after 64Cu-ATSM injection. The maximum percentage of the injected dose per gram of tissue was higher in the operation group (0.047±0.015 vs. 0.026±0.006, p=0.021). The fundus/liver ratio was also higher in the operation group (0.541±0.126 vs. 0.278±0.049, p=0.002). Upon autoradiography, 64Cu-ATSM uptake was observed in the fundus in the operation group, and was well-correlated to that observed on the PET image. Upon immunohistochemistry, expression of hypoxia-inducible factor 1a and pimonidazole were significantly increased at the fundus and lesser curvature compared to the greater curvature in the operation group.
  
  
  CONCLUSIONS
  Hypoxia PET imaging with 64Cu-ATSM can detect ischemia in a rat esophagectomy model. Further clinical studies are needed to verify whether hypoxia imaging may be useful in humans.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Yonsei University, College of Medicine, Seoul, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Ajou University, School of Medicine, Suwon, Republic of Korea.
authors.forename: Seong Yong
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Kang
authors.affiliation: Department of Nuclear Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Arthur
authors.initials: A
authors.lastname: Cho
authors.affiliation: Department of Nuclear Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Ju Ri
authors.initials: JR
authors.lastname: Chae
authors.affiliation: Department of Nuclear Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Ye Lim
authors.initials: YL
authors.lastname: Cho
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Yonsei University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Young
authors.initials: KY
authors.lastname: Chung
mesh_terms: D057868:Anastomotic Leak / Q000000981:diagnostic imaging / Q000209:etiology; D000818:Animals; D001345:Autoradiography; D056831:Coordination Complexes; D003301:Copper Radioisotopes; D016629:Esophagectomy / Q000009:adverse effects*; D004943:Esophagogastric Junction / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000473:pathology; D005748:Gastric Fundus / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007511:Ischemia / Q000000981:diagnostic imaging* / Q000209:etiology* / Q000473:pathology; D008297:Male; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013882:Thiosemicarbazones
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009593:Nitroimidazoles; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); C033815:pimonidazole