(18)F-PEG1-Vinyl Sulfone-Labeled Red Blood Cells as Positron Emission Tomography Agent to Image Intra-Abdominal Bleeding

(18)F-Labeled blood pool agents (BPAs) have attracted great attention for identifying bleeding sites. However, many BPAs are not sufficiently evaluated partially due to the limitations of labeling methods. In our previous work, we noticed that (18)F-PEG1-vinyl sulfone ((18)F-VS) could efficiently label red blood cells (RBCs) ex vivo and in situ. However, its application as BPA is not fully evaluated. In this study, we systematically explored the feasibility of using (18)F-VS-labeled RBCs as a positron emission tomography (PET) BPA for intra-abdominal bleeding diagnosis. In brief, we first optimized the labeling conditions, which lead to an 80% labeling yield of RBCs after incubating with (18)F-VS in phosphate-buffered saline (PBS) at 37°C for 20 min. (18)F-VS-labeled RBCs were found to be stable in vitro, which could simplify its transportation/storage for in vivo applications. In normal rat PET study, the cardiovascular system could be clearly imaged up to 5 h post injection (p.i.). An intra-abdominal hemorrhage rat model demonstrated that the (18)F-VS-labeled RBCs clearly showed the dynamic changes of extravascular radioactivity due to intra-abdominal hemorrhage. Validation in the model of gastrointestinal bleeding clearly demonstrated the great potential of using (18)F-VS-labeled RBCs as a BPA, which could be further evaluated in future studies.