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

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

Kyungpook National University

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English
Article number	102375
Journal	Blood Cells, Molecules, and Diseases
Volume	80
DOIs	https://doi.org/10.1016/j.bcmd.2019.102375
State	Published - Feb 2020

Keywords

Extracellular vesicles-mimetics
Gamma camera
Inflammation
Red blood cell
Technetium-99m
White blood cell

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10.1016/j.bcmd.2019.102375

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Son, S. H., Oh, J. M., Gangadaran, P., Ji, H. D., Lee, H. W., Rajendran, R. L., Baek, S. H., Gopal, A., Kalimuthu, S., Jeong, S. Y., Lee, S. W., Lee, J., & Ahn, B. C. (2020). White blood cell labeling with Technetium-99m (^99mTc) using red blood cell extracellular vesicles-mimetics. Blood Cells, Molecules, and Diseases, 80, Article 102375. https://doi.org/10.1016/j.bcmd.2019.102375

@article{99b04ac0084b4f349c41c82aeff1d252,

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

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",

author = "Son, {Seung Hyun} and Oh, {Ji Min} and Prakash Gangadaran and Ji, {Hyun Dong} and Lee, {Ho Won} and Rajendran, {Ramya Lakshmi} and Baek, {Se Hwan} and Arunnehru Gopal and Senthilkumar Kalimuthu and Jeong, {Shin Young} and Lee, {Sang Woo} and Jaetae Lee and Ahn, {Byeong Cheol}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2020",

month = feb,

doi = "10.1016/j.bcmd.2019.102375",

language = "English",

volume = "80",

journal = "Blood Cells, Molecules, and Diseases",

issn = "1079-9796",

publisher = "Academic Press Inc.",

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TY - JOUR

T1 - White blood cell labeling with Technetium-99m (99mTc) using red blood cell extracellular vesicles-mimetics

AU - Son, Seung Hyun

AU - Oh, Ji Min

AU - Gangadaran, Prakash

AU - Ji, Hyun Dong

AU - Lee, Ho Won

AU - Rajendran, Ramya Lakshmi

AU - Baek, Se Hwan

AU - Gopal, Arunnehru

AU - Kalimuthu, Senthilkumar

AU - Jeong, Shin Young

AU - Lee, Sang Woo

AU - Lee, Jaetae

AU - Ahn, Byeong Cheol

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - Extracellular vesicles-mimetics

KW - Gamma camera

KW - Inflammation

KW - Red blood cell

KW - Technetium-99m

KW - White blood cell

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U2 - 10.1016/j.bcmd.2019.102375

DO - 10.1016/j.bcmd.2019.102375

M3 - Article

C2 - 31655394

AN - SCOPUS:85073735005

SN - 1079-9796

VL - 80

JO - Blood Cells, Molecules, and Diseases

JF - Blood Cells, Molecules, and Diseases

M1 - 102375

ER -

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

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