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PLoS One. 2015 Apr 22;10(4):e0124665. doi: 10.1371/journal.pone.0124665. eCollection 2015.

A Comparative pO2 Probe and [18F]-Fluoro-Azomycinarabino-Furanoside ([18F]FAZA) PET Study Reveals Anesthesia-Induced Impairment of Oxygenation and Perfusion in Tumor and Muscle.

Author information

1
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
2
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany; Department of Dermatology, Eberhard Karls University Tübingen, Liebermeisterstraße 25, 72076 Tübingen, Germany.
3
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany; Department of Radiology, Eberhard Karls University Tübingen, Hoppe-Seyler-Straße 3, 72076 Tübingen, Germany.
4
Department of Physiology, Eberhard Karls University Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
5
Institute for Clinical Epidemiology and Applied Biometry, Eberhard Karls University Tübingen, Silcherstraße 5, 72076 Tübingen, Germany.
6
Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tübingen, Hoppe-Seyler-Straße 3, 72076 Tübingen, Germany.

Abstract

METHODS:

CT26 colon carcinoma-bearing mice were anesthetized with isoflurane (IF) or ketamine/xylazine (KX) while breathing air or oxygen (O2). We performed 10 min static PET scans 1 h, 2 h and 3 h after [18F]FAZA injection and calculated the [18F]FAZA-uptake and tumor-to-muscle ratios (T/M). In another experimental group, we placed a pO2 probe in the tumor as well as in the gastrocnemius muscle to measure the pO2 and perfusion.

RESULTS:

Ketamine/xylazine-anesthetized mice yielded up to 3.5-fold higher T/M-ratios compared to their isoflurane-anesthetized littermates 1 h, 2 h and 3 h after [18F]FAZA injection regardless of whether the mice breathed air or oxygen (3 h, KX-air: 7.1 vs. IF-air: 1.8, p = 0.0001, KX-O2: 4.4 vs. IF-O2: 1.4, p < 0.0001). The enhanced T/M-ratios in ketamine/xylazine-anesthetized mice were mainly caused by an increased [18F]FAZA uptake in the carcinomas. Invasive pO2 probe measurements yielded enhanced intra-tumoral pO2 values in air- and oxygen-breathing ketamine/xylazine-anesthetized mice compared to isoflurane-anesthetized mice (KX-air: 1.01 mmHg, IF-air: 0.45 mmHg; KX-O2 9.73 mmHg, IF-O2: 6.25 mmHg). Muscle oxygenation was significantly higher in air-breathing isoflurane-anesthetized (56.9 mmHg) than in ketamine/xylazine-anesthetized mice (33.8 mmHg, p = 0.0003).

CONCLUSION:

[18F]FAZA tumor uptake was highest in ketamine/xylazine-anesthetized mice regardless of whether the mice breathed air or oxygen. The generally lower [18F]FAZA whole-body uptake in isoflurane-anesthetized mice could be due to the higher muscle pO2-values in these mice compared to ketamine/xylazine-anesthetized mice. When performing preclinical in vivo hypoxia PET studies, oxygen should be avoided, and ketamine/xylazine-anesthesia might alleviate the identification of tumor hypoxia areals.

PMID:
25902054
PMCID:
PMC4406741
DOI:
10.1371/journal.pone.0124665
[Indexed for MEDLINE]
Free PMC Article

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