Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using (99m)Tc-HMPAO.
Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with (99m)Tc-HMPAO under physiologic conditions and monitored in vivo distribution of (99m)Tc-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with (99m)Tc-HMPAO for 1 hr incubation, followed by removal of free (99m)Tc-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with (99m)Tc-HMPAO, the radiochemical purity of (99m)Tc-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in (99m)Tc-HMPAO-ENVs. (99m)Tc-HMPAO-ENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5 hr. SPECT/CT images of the mice injected with (99m)Tc-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with (99m)Tc-HMPAO showed high brain uptake until 5 hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea.
Do Won
DW
Hwang
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea.
Hongyoon
H
Choi
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea.|Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, 405 30 Gothenburg, Sweden.
Su Chul
SC
Jang
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Min Young
MY
Yoo
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Ji Yong
JY
Park
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Na Eun
NE
Choi
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea.
Hyun Jeong
HJ
Oh
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea.
Seunggyun
S
Ha
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea.
Yun-Sang
YS
Lee
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jae Min
JM
Jeong
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea.
Yong Song
YS
Gho
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea.
Dong Soo
DS
Lee
D000818:Animals; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry; D055354:Exosomes / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013194:Staining and Labeling / Q000379:methods*; D019690:Technetium Tc 99m Exametazime / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D004337:Drug Carriers; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime