title: 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.
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).
  
  
  CONCLUSIONS
  [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.
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Mahling
authors.affiliation: 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.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Fuchs
authors.affiliation: 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.
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Thaiss
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
authors.forename: Florian C
authors.initials: FC
authors.lastname: Maier
authors.affiliation: Department of Physiology, Eberhard Karls University Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Feger
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bukala
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Harant
authors.affiliation: Institute for Clinical Epidemiology and Applied Biometry, Eberhard Karls University Tübingen, Silcherstraße 5, 72076 Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eichner
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Eberhard Karls University Tübingen, Hoppe-Seyler-Straße 3, 72076 Tübingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Reutershan
authors.affiliation: Department of Physiology, Eberhard Karls University Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Reischl
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.affiliation: 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.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kneilling
mesh_terms: D000758:Anesthesia / Q000009:adverse effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D007530:Isoflurane / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D015335:Molecular Probes / Q000378:metabolism*; D009132:Muscles / Q000000981:diagnostic imaging* / Q000187:drug effects; D009369:Neoplasms / Q000000981:diagnostic imaging*; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D010477:Perfusion; D049268:Positron-Emission Tomography; D012119:Respiration / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D014991:Xylazine / Q000494:pharmacology
chemical_list: D015335:Molecular Probes; D009593:Nitroimidazoles; C498052:fluoroazomycin arabinoside; D014991:Xylazine; D007649:Ketamine; D007530:Isoflurane; D010100:Oxygen