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

Park SY, Kang WJ, Cho A, Chae JR, Cho YL, Kim JY, Lee JW, Chung KY - PLoS ONE (2015)

Bottom Line: 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.Further clinical studies are needed to verify whether hypoxia imaging may be useful in humans.

View Article: PubMed Central - PubMed

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.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Operative view.A. Normal vascular anatomoy of rat. B. Partial devascularization was done by ligating the left gastric artery and short gastric arteries. C. The esophageal-gastric junction was then incised around 50% of the circumference, leaving the small bridge of tissue at posterior part of esophagogastric junction. D. The esophagogastric anastomosis was sutured with interrupted 5–0 polypropylene sutures. E. Operative pictures after all procedures in operation group. F. After microPET imaging, the stomach was incised along the lesser curvature to obtain autoradiographic images.
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pone.0131083.g001: Operative view.A. Normal vascular anatomoy of rat. B. Partial devascularization was done by ligating the left gastric artery and short gastric arteries. C. The esophageal-gastric junction was then incised around 50% of the circumference, leaving the small bridge of tissue at posterior part of esophagogastric junction. D. The esophagogastric anastomosis was sutured with interrupted 5–0 polypropylene sutures. E. Operative pictures after all procedures in operation group. F. After microPET imaging, the stomach was incised along the lesser curvature to obtain autoradiographic images.

Mentions: The current study was approved by the institutional Animal Care and Use Committee (No. 2013–0350) of Yonsei University, College of Medicine. Based on previous studies, a rat esophagectomy model was created using 12-16-week old, 300-350-g, male Sprague-Dawley rats [6,7]. Twelve rats were housed (3 per cage) in conventional suspension cages, and given food and water ad libitum until the time of surgery. Six rats were each randomly assigned to the control (n = 6) and the operation groups (n = 6). In all rats, a 3-cm median laparotomy incision was made under inhaled sevoflurane anesthesia using a rodent ventilator. In the operation group, partial gastric devascularization was performed by ligating the left gastric artery and the short gastric arteries (Fig 1A and 1B). The esophageal-gastric junction was then incised around 50% of the circumference. This left a small bridge of tissue at posterior part of esophagogastric junction for simplifying the anastomotic suturing. The esophagogastric anastomosis was sutured with interrupted 5–0 polypropylene sutures (Fig 1C, 1D and 1E). All laparotomy incisions were closed with continuous 3–0 silk sutures. Animals were allowed free access to water only after operation. The control group underwent only incision of the esophageal-gastric junction; suturing was performed without partial gastric devascularization.


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

Park SY, Kang WJ, Cho A, Chae JR, Cho YL, Kim JY, Lee JW, Chung KY - PLoS ONE (2015)

Operative view.A. Normal vascular anatomoy of rat. B. Partial devascularization was done by ligating the left gastric artery and short gastric arteries. C. The esophageal-gastric junction was then incised around 50% of the circumference, leaving the small bridge of tissue at posterior part of esophagogastric junction. D. The esophagogastric anastomosis was sutured with interrupted 5–0 polypropylene sutures. E. Operative pictures after all procedures in operation group. F. After microPET imaging, the stomach was incised along the lesser curvature to obtain autoradiographic images.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476727&req=5

pone.0131083.g001: Operative view.A. Normal vascular anatomoy of rat. B. Partial devascularization was done by ligating the left gastric artery and short gastric arteries. C. The esophageal-gastric junction was then incised around 50% of the circumference, leaving the small bridge of tissue at posterior part of esophagogastric junction. D. The esophagogastric anastomosis was sutured with interrupted 5–0 polypropylene sutures. E. Operative pictures after all procedures in operation group. F. After microPET imaging, the stomach was incised along the lesser curvature to obtain autoradiographic images.
Mentions: The current study was approved by the institutional Animal Care and Use Committee (No. 2013–0350) of Yonsei University, College of Medicine. Based on previous studies, a rat esophagectomy model was created using 12-16-week old, 300-350-g, male Sprague-Dawley rats [6,7]. Twelve rats were housed (3 per cage) in conventional suspension cages, and given food and water ad libitum until the time of surgery. Six rats were each randomly assigned to the control (n = 6) and the operation groups (n = 6). In all rats, a 3-cm median laparotomy incision was made under inhaled sevoflurane anesthesia using a rodent ventilator. In the operation group, partial gastric devascularization was performed by ligating the left gastric artery and the short gastric arteries (Fig 1A and 1B). The esophageal-gastric junction was then incised around 50% of the circumference. This left a small bridge of tissue at posterior part of esophagogastric junction for simplifying the anastomotic suturing. The esophagogastric anastomosis was sutured with interrupted 5–0 polypropylene sutures (Fig 1C, 1D and 1E). All laparotomy incisions were closed with continuous 3–0 silk sutures. Animals were allowed free access to water only after operation. The control group underwent only incision of the esophageal-gastric junction; suturing was performed without partial gastric devascularization.

Bottom Line: 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.Further clinical studies are needed to verify whether hypoxia imaging may be useful in humans.

View Article: PubMed Central - PubMed

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.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus