Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using 99mTc-HMPAO

• Published in: Scientific reports Vol. 5; no. 1; p. 15636
• Main Authors: Hwang, Do Won, Choi, Hongyoon, Jang, Su Chul, Yoo, Min Young, Park, Ji Yong, Choi, Na Eun, Oh, Hyun Jeong, Ha, Seunggyun, Lee, Yun-Sang, Jeong, Jae Min, Gho, Yong Song, Lee, Dong Soo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 26.10.2015
• Subjects: Biodistribution; CD63 antigen; Computed tomography; Drug delivery; Exosomes; Intravenous administration; Labeling; Liver; Macrophages; Medicine; Methods; Nanoparticles; Neuroimaging; Proteins; Roles; Single photon emission computed tomography
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep15636

Abstract 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.