White blood cell labeling with Technetium-99m (99mTc) using red blood cell extracellular vesicles-mimetics

Seung Hyun Son; Ji Min Oh; Prakash Gangadaran; Hyun Dong Ji; Ho Won Lee; Ramya Lakshmi Rajendran; Se Hwan Baek; Arunnehru Gopal; Senthilkumar Kalimuthu; Shin Young Jeong; Sang-Woo Lee; Jaetae Lee; Byeong-Cheol Ahn

doi:10.1016/j.bcmd.2019.102375

White blood cell labeling with Technetium-99m (^99mTc) using red blood cell extracellular vesicles-mimetics

Blood Cells Mol Dis. 2020 Feb:80:102375. doi: 10.1016/j.bcmd.2019.102375. Epub 2019 Oct 20.

Affiliations

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.

PMID: 31655394
DOI: 10.1016/j.bcmd.2019.102375

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.

Keywords: Extracellular vesicles-mimetics; Gamma camera; Inflammation; Red blood cell; Technetium-99m; White blood cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Tracking
Disease Models, Animal
Erythrocytes / metabolism*
Extracellular Vesicles / metabolism*
Extracellular Vesicles / ultrastructure
Female
Inflammation / diagnostic imaging
Inflammation / etiology
Inflammation / metabolism
Leukocytes / metabolism*
Mice
Molecular Imaging / methods
Radiopharmaceuticals / metabolism*
Rats
Staining and Labeling
Subcellular Fractions
Technetium / metabolism*
Tissue Distribution

Substances

Radiopharmaceuticals
Technetium