TY - JOUR
T1 - Copper-64 Labeled PEGylated Exosomes for In Vivo Positron Emission Tomography and Enhanced Tumor Retention
AU - Shi, Sixiang
AU - Li, Tingting
AU - Wen, Xiaofei
AU - Wu, Sherry Y.
AU - Xiong, Chiyi
AU - Zhao, Jun
AU - Lincha, Victor R.
AU - Chow, Diana S.
AU - Liu, Yiyao
AU - Sood, Anil K.
AU - Li, Chun
N1 - Funding Information:
S.S. was supported by the John S. Dunn Sr. Distinguished Chair Fund in Diagnostic Imaging. This work was conducted at the MD Anderson Center for Advanced Biomedical Imaging in part with equipment support from General Electric Healthcare. Portions of this work were supported by the National Institutes of Health (NIH) (P50CA217685, P50CA098258, and R35CA209904), the American Cancer Society Research Professor Award, and the Frank McGraw Memorial Chair in Cancer Research. S.Y.W. was supported by Ovarian Cancer Research Fund Alliance, Foundation for Women’s Cancer, and Cancer Prevention and Research Institute of Texas training Grants (RP101502 and RP101489). X.W. was supported in part by the China Postdoctoral Science Foundation Grant (2018M641851) and Hei Long Jiang Postdoctoral Foundation (LBH-Z18139). The Research Animal Support Facility, High Resolution Electron Microscopy Facility, and Small Animal Imaging Facility are supported by a Cancer Center Support Grant from the National Institutes of Health (P30CA016672). We thank K. Hale from Scientific Publications Services at MD Anderson Cancer Center for editing the manuscript.
Publisher Copyright:
© 2019 American Chemical Society.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/10/16
Y1 - 2019/10/16
N2 - Exosomes have attracted tremendous attention due to their important role in physiology, pathology, and oncology, as well as promising potential in biomedical applications. Although great efforts have been dedicated to investigating their biological properties and applications as natural cancer drug-delivery systems, the systemic biodistribution of exosomes remains underexplored. In addition, exosome-based drug delivery is inevitably hindered by the robust liver clearance, leading to suboptimal tumor retention and therapeutic efficiency. In this study, we report one of the first examples using in vivo positron emission tomography (PET) for noninvasive monitoring of copper-64 (64Cu)-radiolabeled polyethylene glycol (PEG)-modified exosomes, achieving excellent imaging quality and quantitative measurement of blood residence and tumor retention. PEGylation not only endowed exosomes with a superior pharmacokinetic profile and great accumulation in the tumor versus traditionally reported native exosomes but also reduced premature hepatic sequestration and clearance of exosomes, findings that promise enhanced therapeutic delivery efficacy and safety in future studies. More importantly, this study provides important guidelines about surface engineering, radiochemistry, and molecular imaging in obtaining accurate and quantitative biodistribution information on exosomes, which may benefit future exploration in the realm of exosomes.
AB - Exosomes have attracted tremendous attention due to their important role in physiology, pathology, and oncology, as well as promising potential in biomedical applications. Although great efforts have been dedicated to investigating their biological properties and applications as natural cancer drug-delivery systems, the systemic biodistribution of exosomes remains underexplored. In addition, exosome-based drug delivery is inevitably hindered by the robust liver clearance, leading to suboptimal tumor retention and therapeutic efficiency. In this study, we report one of the first examples using in vivo positron emission tomography (PET) for noninvasive monitoring of copper-64 (64Cu)-radiolabeled polyethylene glycol (PEG)-modified exosomes, achieving excellent imaging quality and quantitative measurement of blood residence and tumor retention. PEGylation not only endowed exosomes with a superior pharmacokinetic profile and great accumulation in the tumor versus traditionally reported native exosomes but also reduced premature hepatic sequestration and clearance of exosomes, findings that promise enhanced therapeutic delivery efficacy and safety in future studies. More importantly, this study provides important guidelines about surface engineering, radiochemistry, and molecular imaging in obtaining accurate and quantitative biodistribution information on exosomes, which may benefit future exploration in the realm of exosomes.
UR - http://www.scopus.com/inward/record.url?scp=85073213561&partnerID=8YFLogxK
U2 - 10.1021/acs.bioconjchem.9b00587
DO - 10.1021/acs.bioconjchem.9b00587
M3 - Journal article
C2 - 31560538
AN - SCOPUS:85073213561
SN - 1043-1802
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
ER -