(18)F-fluorodeoxyglucose positron emission tomography–computed tomography for assessing organ distribution of stressed red blood cells in mice

Red blood cells (RBCs) stressed by high temperature are similar to senescent or damaged RBCs in pathological conditions. RBCs can be efficiently labelled with (18)F-fluorodeoxyglucose (FDG). The aim of this study was to assess stressed RBCs erythrophagocytosis and organ distribution in vivo with the application of (18)F-FDG PET/CT. RBCs were induced under high temperature (48 °C) to prepare stressed RBCs. Fluorescence-activated cell sorting (FACS) was used to analyse reactive oxygen species (ROS) generation, intracellular Ca(2+) concentration and membrane phosphatidylserine (PS) externalization of RBCs. (18)F-FDG was used to label RBCs and assess the erythrophagocytosis. Finally, (18)F-FDG PET/CT was applied to reveal and measure the organ distribution of stressed RBCs in mice. Compared with untreated RBCs, stressed RBCs decreased in cell volume and increased in ROS level, intracellular Ca(2+) concentration, and PS exposure. RBCs could be labelled by (18)F-FDG. Stressed RBCs tended to be phagocytosed by macrophages via assessment of FACS and radioactivity. (18)F-FDG PET/CT imaging showed that stressed RBCs were mainly trapped in spleen, while untreated RBCs remained in circulation system. Thus, stressed RBCs can be effectively labelled by (18)F-FDG and tend to be trapped in spleen of mice as assessed by PET/CT.