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64Cu-ATSM Hypoxia Positron Emission Tomography for Detection of Conduit Ischemia in an Experimental Rat Esophagectomy Model

 Seong Yong Park  ;  Won Jun Kang  ;  Arthur Cho  ;  Ju Ri Chae  ;  Ye Lim Cho  ;  Jung Young Kim  ;  Ji Woong Lee  ;  Kyung Young Chung 
 PLOS ONE, Vol.10(6) : e0131083, 2015 
Journal Title
Issue Date
Anastomotic Leak/diagnostic imaging ; Anastomotic Leak/etiology ; Animals ; Autoradiography ; Copper Radioisotopes ; Esophagectomy/adverse effects* ; Esophagogastric Junction/blood supply* ; Esophagogastric Junction/diagnostic imaging* ; Esophagogastric Junction/pathology ; Gastric Fundus/blood supply ; Gastric Fundus/diagnostic imaging ; Gastric Fundus/pathology ; Hypoxia/diagnostic imaging ; Hypoxia/etiology ; Hypoxia/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Immunohistochemistry ; Ischemia/diagnostic imaging* ; Ischemia/etiology* ; Ischemia/pathology ; Male ; Nitroimidazoles/pharmacokinetics ; Organometallic Compounds ; Positron-Emission Tomography/methods* ; Rats ; Rats, Sprague-Dawley ; Thiosemicarbazones
BACKGROUND: We designed a hypoxia-imaging modality to detect ischemia of the gastric conduit after esophagectomy. MATERIALS AND 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. CONCLUSION: 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.
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1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Won Jun(강원준) ORCID logo https://orcid.org/0000-0002-2107-8160
Park, Seong Yong(박성용) ORCID logo https://orcid.org/0000-0002-5180-3853
Chung, Kyung Young(정경영)
Cho, Arthur Eung Hyuck(조응혁) ORCID logo https://orcid.org/0000-0001-8670-2473
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