title: Oxygen breathing affects 3'-deoxy-3'-18F-fluorothymidine uptake in mouse models of arthritis and cancer.
abstract: Noninvasive in vivo imaging of biologic processes using PET is an important tool in preclinical studies. We observed significant differences in 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) uptake in arthritic ankles and carcinomas between dynamic and static PET measurements when mice breathed oxygen. Thus, we suspected that air or oxygen breathing and the anesthesia protocol might influence (18)F-FLT tracer uptake.
  
  
  METHODS
  We injected arthritic, healthy, and CT26 colon carcinoma-bearing mice with (18)F-FLT before static or dynamic small-animal PET measurements. The spontaneously oxygen- or air-breathing mice were kept conscious or anesthetized with ketamine and xylazine during (18)F-FLT uptake before the 10-min static PET measurements. For dynamic PET scans, mice were anesthetized during the entire measurement. (18)F-FLT uptake was reported in percentage injected dose per cubed centimeter by drawing regions of interest around ankles, carcinomas, and muscle tissue. Additionally, venous blood samples were collected before (18)F-FLT injection and after PET measurement to analyze pH, carbon dioxide partial pressure (pCO(2)), and lactate values.
  
  
  RESULTS
  A significantly reduced (18)F-FLT uptake was measured in arthritic ankles and in CT26 colon carcinomas when the mice breathed oxygen and were conscious during tracer uptake, compared with mice that were anesthetized during (18)F-FLT uptake. Breathing air completely abolished this phenomenon. Analysis of blood samples that were obtained from the mice before (18)F-FLT injection and after the PET scan implicated respiratory acidosis that was induced by oxygen breathing and consciousness during tracer uptake. Acidosis was found to be the primary factor responsible for the reduced (18)F-FLT uptake, as reflected by increased pCO(2) and reduced pH and lactate values.
  
  
  CONCLUSIONS
  Oxygen-breathing conscious mice sustained respiratory acidosis and, consequently, reduced cell proliferation and (18)F-FLT uptake in arthritic ankles and CT26 colon carcinomas. Thus, we suggest the use of air instead of oxygen breathing for (18)F-FLT PET measurements.
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Fuchs
authors.forename: Damaris
authors.initials: D
authors.lastname: Kukuk
authors.forename: Gerald
authors.initials: G
authors.lastname: Reischl
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Martin
authors.initials: M
authors.lastname: Eichner
authors.forename: Jörg
authors.initials: J
authors.lastname: Reutershan
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.forename: Manfred
authors.initials: M
authors.lastname: Kneilling
mesh_terms: D000758:Anesthesia; D000818:Animals; D000842:Ankle / Q000000981:diagnostic imaging; D001168:Arthritis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D016477:Artifacts; D001692:Biological Transport / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003243:Consciousness; D015224:Dideoxynucleosides / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D012119:Respiration; D014991:Xylazine / Q000494:pharmacology
chemical_list: D015224:Dideoxynucleosides; D002245:Carbon Dioxide; D014991:Xylazine; D019344:Lactic Acid; D007649:Ketamine; D005956:Glucose-6-Phosphate Isomerase; C002854:alovudine; D010100:Oxygen