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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

Immunohistochemistry.A. HIF-1a expression in the fundus of the operation group. B. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were expressed in the fundus. C. HIF-1a expression in the fundus of the control group. D. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were not expressed in the fundus. E. Comparison of HIF-1a expression levels between the fundus and greater curvature in each group. F. Comparison of pimonidazole expression levels between the fundus and greater curvature in each group. HIF-1a and pimonidazole expression was significantly higher in the fundus than the greater curvature in the operation group.
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pone.0131083.g004: Immunohistochemistry.A. HIF-1a expression in the fundus of the operation group. B. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were expressed in the fundus. C. HIF-1a expression in the fundus of the control group. D. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were not expressed in the fundus. E. Comparison of HIF-1a expression levels between the fundus and greater curvature in each group. F. Comparison of pimonidazole expression levels between the fundus and greater curvature in each group. HIF-1a and pimonidazole expression was significantly higher in the fundus than the greater curvature in the operation group.

Mentions: The expression levels of pimonidazole and HIF-1a in the fundus and greater curvature were compared. In the operation group, pimonidazole and HIF-1a were expressed in the fundus but not the greater curvature (Fig 4A and 4B). In the control group, pimonidazole and HIF-1a expression was observed in neither the fundus nor the greater curvature (Fig 4C and 4D). In the operation group, pimonidazole 1 and HIF-1a expression was significantly higher in the fundus than the greater curvature (Fig 4E and 4F).


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)

Immunohistochemistry.A. HIF-1a expression in the fundus of the operation group. B. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were expressed in the fundus. C. HIF-1a expression in the fundus of the control group. D. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were not expressed in the fundus. E. Comparison of HIF-1a expression levels between the fundus and greater curvature in each group. F. Comparison of pimonidazole expression levels between the fundus and greater curvature in each group. HIF-1a and pimonidazole expression was significantly higher in the fundus than the greater curvature in the operation group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131083.g004: Immunohistochemistry.A. HIF-1a expression in the fundus of the operation group. B. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were expressed in the fundus. C. HIF-1a expression in the fundus of the control group. D. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were not expressed in the fundus. E. Comparison of HIF-1a expression levels between the fundus and greater curvature in each group. F. Comparison of pimonidazole expression levels between the fundus and greater curvature in each group. HIF-1a and pimonidazole expression was significantly higher in the fundus than the greater curvature in the operation group.
Mentions: The expression levels of pimonidazole and HIF-1a in the fundus and greater curvature were compared. In the operation group, pimonidazole and HIF-1a were expressed in the fundus but not the greater curvature (Fig 4A and 4B). In the control group, pimonidazole and HIF-1a expression was observed in neither the fundus nor the greater curvature (Fig 4C and 4D). In the operation group, pimonidazole 1 and HIF-1a expression was significantly higher in the fundus than the greater curvature (Fig 4E and 4F).

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