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

Xinyi Zhang; Li Wang; Wenhui Fu; Yue Feng; Chengrun Zeng; Liu Zhou; Tao Zhang; Tingting Xu; Jianpeng Cao; Zibo Li; Yue Chen

doi:10.3389/fmed.2021.646862

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

Front Med (Lausanne). 2021 Jul 5:8:646862. doi: 10.3389/fmed.2021.646862. eCollection 2021.

Authors

Xinyi Zhang^{1

2

3}, Li Wang^{1

2

3}, Wenhui Fu^{1

2

3}, Yue Feng^{1

2

3}, Chengrun Zeng^{1

2

3}, Liu Zhou^{1

2

3

4}, Tao Zhang⁵, Tingting Xu^{1

2

3}, Jianpeng Cao^{1

2

3}, Zibo Li⁵, Yue Chen^{1

2

3}

Affiliations

¹ Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
² Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan, Luzhou, China.
³ Academician (Expert) Workstation of Sichuan, Luzhou, China.
⁴ School of Pharmacy, Southwest Medical University, Luzhou, China.
⁵ Department of Radiology, Lineberger Comprehensive Cancer Center, and Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, United States.

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.

Keywords: 18F-vinyl sulfone; blood pool imaging; intra-abdominal hemorrhage; positron emission tomography (PET); red blood cell.