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

Abstract

18F-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 18F-PEG1-vinyl sulfone (18F-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 18F-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 18F-VS in phosphate-buffered saline (PBS) at 37°C for 20 min. 18F-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 18F-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 18F-VS-labeled RBCs as a BPA, which could be further evaluated in future studies.

68Ga-Labeled Maleimide for Blood Pool and Lymph PET Imaging through Covalent Bonding to Serum Albumin In Vivo

“…The establishment of the transient micro-bleeding model is according to the procedure of the published literature. 35 Before the experiment, rats had fasted for 12 h, and an 18-gauge needle was inserted through the anus to puncture the rectum wall, resulting in temporary bleeding. Blood on the tip of the needle could be seen when the needle was removed.…”

From molecules to medicine: thiol selective bioconjugation in synthesis of diagnostic and therapeutic radiopharmaceuticals

“…The uptake of 18 F-PEG 1 -VS is presumed to be related to the presence of free thiol groups in brain tissues. This suggests that brain imaging can be performed using this precursor 62 . Using a similar approach, Wu et al synthesized a series of PSMA-targeting tracers using 18 F-(PEG) n -VS prosthetic groups (Figure 15 A).…”