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Abstract
BACKGROUND:
Extracellular vesicles, have gained increasing attention for their application in drug delivery. Here, we developed a novel method for radiolabeling WBCs with 99mTc using RBC-derived extracellular vesicles -mimetics (EVMs), and monitored in vivo inflammation tracking of 99mTc-WBC using gamma camera in acute inflammation mouse model.

METHODS:
Engineered EVMs from RBCs were produced by a one-step extrusion method. RBC-EVMs were analyzed by NTA and TEM. Cells were labeled with 99mTc by using 99mTc-RBC-EVMs. Inflammation mice model was prepared and confirmed by 18F-FDG PET/CT. 99mTc-WBCs were injected in mice, and their biodistribution was analyzed by gamma camera.

FINDING:
The radiochemical purity of 99mTc-RBC-EVMs was 100%. The 99mTc-labeling did't affect the size and morphology. The 99mTc in the cytoplasm of RBC-EVMs was successfully confirmed by high angle annular dark field STEM (scanning transmission electron microscope). Cells were successfully labeled with 99mTc using 99mTc-RBC-EVMs, and the counts per minute was increased in dose- and time-dependent manners. The 18F-FDG PET/CT images confirmed establishment of acute inflammation (left mouse foot). 99mTc-WBCs showed higher uptake in the inflamed foot than non-inflamed foot.

INTERPRETATION:
This novel method for radiolabeling WBCs using RBC-EVMs. 99mTc labeling may be a feasible method to monitor the in vivo biodistribution of cells.

Author information

Son SH1, Oh JM1, Gangadaran P2, Ji HD1, Lee HW1, Rajendran RL2, Baek SH1, Gopal A1, Kalimuthu S1, Jeong SY1, Lee SW1, Lee J1, Ahn BC3.
1
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
2
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
3
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: abc2000@knu.ac.kr.