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 39-deoxy-39-18F-fluorothymidine (18F-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 18F-FLT tracer uptake. Methods: We injected arthritic, healthy, and CT26 colon carcinoma-bearing mice with 18F-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 18F-FLT uptake before the 10-min static PET measurements. For dynamic PET scans, mice were anesthetized during the entire measurement. 18F-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 18F-FLT injection and after PET measurement to analyze pH, carbon dioxide partial pressure (pCO2), and lactate values. Results: A significantly reduced 18F-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 18F-FLT uptake. Breathing air completely abolished this phenomenon. Analysis of blood samples that were obtained from the mice before 18F-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 18F-FLT uptake, as reflected by increased pCO 2 and reduced pH and lactate values. Conclusion: Oxygen-breathing conscious mice sustained respiratory acidosis and, consequently, reduced cell proliferation and 18F-FLT uptake in arthritic ankles and CT26 colon carcinomas. Thus, we suggest the use of air instead of oxygen breathing for 18F-FLT PET measurements. Copyright © 2012 by the Society of Nuclear Medicine, Inc.