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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

The correlations between expression of immunohistochemistry and PET parameters.A. HIF-1a expression and %ID/g (Pearson correlation 0.534, p<0.001). B. HIF-1a expression and Fundus/Liver ratio (Pearson correlation 0.593, p<0.001). C. Pimonidazole expression and %ID/g (Pearson correlation 0.386, p = 0.007). D. Pimonidazole expression and Fundus/Liver ratio (Pearson correlation 0.483, p = 0.001).
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pone.0131083.g005: The correlations between expression of immunohistochemistry and PET parameters.A. HIF-1a expression and %ID/g (Pearson correlation 0.534, p<0.001). B. HIF-1a expression and Fundus/Liver ratio (Pearson correlation 0.593, p<0.001). C. Pimonidazole expression and %ID/g (Pearson correlation 0.386, p = 0.007). D. Pimonidazole expression and Fundus/Liver ratio (Pearson correlation 0.483, p = 0.001).

Mentions: The correlations between expression of immunohistochemistry and PET parameters were analysed. HIF-1a expression was correlated with both %ID/g and Fundus/Liver ratio (Pearson correlation 0.534, p<0.001 and Pearson correlation 0.593, p<0.001, respectively. Fig 5A and 5B). Pimonidazole expression was also correlated with both %ID/g and Fundus/Liver ratio (Pearson correlation 0.386, p = 0.007 and Pearson correlation 0.483, p = 0.001, respectively. Fig 5C and 5D).


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)

The correlations between expression of immunohistochemistry and PET parameters.A. HIF-1a expression and %ID/g (Pearson correlation 0.534, p<0.001). B. HIF-1a expression and Fundus/Liver ratio (Pearson correlation 0.593, p<0.001). C. Pimonidazole expression and %ID/g (Pearson correlation 0.386, p = 0.007). D. Pimonidazole expression and Fundus/Liver ratio (Pearson correlation 0.483, p = 0.001).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131083.g005: The correlations between expression of immunohistochemistry and PET parameters.A. HIF-1a expression and %ID/g (Pearson correlation 0.534, p<0.001). B. HIF-1a expression and Fundus/Liver ratio (Pearson correlation 0.593, p<0.001). C. Pimonidazole expression and %ID/g (Pearson correlation 0.386, p = 0.007). D. Pimonidazole expression and Fundus/Liver ratio (Pearson correlation 0.483, p = 0.001).
Mentions: The correlations between expression of immunohistochemistry and PET parameters were analysed. HIF-1a expression was correlated with both %ID/g and Fundus/Liver ratio (Pearson correlation 0.534, p<0.001 and Pearson correlation 0.593, p<0.001, respectively. Fig 5A and 5B). Pimonidazole expression was also correlated with both %ID/g and Fundus/Liver ratio (Pearson correlation 0.386, p = 0.007 and Pearson correlation 0.483, p = 0.001, respectively. Fig 5C and 5D).

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