TY - JOUR
T1 - Radiolabeled, Antibody-Conjugated Manganese Oxide Nanoparticles for Tumor Vasculature Targeted Positron Emission Tomography and Magnetic Resonance Imaging
AU - Zhan, Yonghua
AU - Shi, Sixiang
AU - Ehlerding, Emily B.
AU - Graves, Stephen A.
AU - Goel, Shreya
AU - Engle, Jonathan W.
AU - Liang, Jimin
AU - Tian, Jie
AU - Cai, Weibo
N1 - Funding Information:
*E-mail: [email protected] (W.C.). *E-mail: [email protected] (J.T.). ORCID Weibo Cai: 0000-0003-4641-0833 Author Contributions †Y.Z. and S.S. contributed equally. The manuscript was written with contributions from all authors. All authors have given approval of the final version of the manuscript. Funding This work was supported, in part, by the University of Wisconsin−Madison; the National Institutes of Health (NIBIB/NCI 1R01CA169365, 1R01CA205101, 1R01EB021336, T32GM008505, T32CA009206, and P30CA014520); the American Cancer Society (125246-RSG-13−099−01-CCE), the National Natural Science Foundation of China under Grants 81227901, 11727813, 81571725, 81230033, 31371006, 61405149, 81660505, and 81627807; the Natural Science Basic Research Plan in Shaanxi Province of China under Grant 2017JM8057; and the Fundamental Research Funds for the Central Universities (JB171204). Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2017 American Chemical Society.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/11/8
Y1 - 2017/11/8
N2 - Manganese oxide nanoparticles (Mn3O4 NPs) have attracted a great deal of attention in the field of biomedical imaging because of their ability to create an enhanced imaging signal in MRI as novel potent T1 contrast agents. In this study, we present tumor vasculature-targeted imaging in mice using Mn3O4 NPs through conjugation to the anti-CD105 antibody TRC105 and radionuclide copper-64 (64Cu, t1/2: 12.7 h). The Mn3O4 conjugated NPs, 64Cu-NOTA-Mn3O4@PEG-TRC105, exhibited sufficient stability in vitro and in vivo. Serial positron emission tomography (PET) and magnetic resonance imaging (MRI) studies evaluated the pharmacokinetics and demonstrated targeting of 64Cu-NOTA-Mn3O4@PEG-TRC105 to 4T1 murine breast tumors in vivo, compared to 64Cu-NOTA-Mn3O4@PEG. The specificity of 64Cu-NOTA-Mn3O4@PEG-TRC105 for the vascular marker CD105 was confirmed through in vivo, in vitro, and ex vivo experiments. Since Mn3O4 conjugated NPs exhibited desirable properties for T1 enhanced imaging and low toxicity, the tumor-specific Mn3O4 conjugated NPs reported in this study may serve as promising multifunctional nanoplatforms for precise cancer imaging and diagnosis.
AB - Manganese oxide nanoparticles (Mn3O4 NPs) have attracted a great deal of attention in the field of biomedical imaging because of their ability to create an enhanced imaging signal in MRI as novel potent T1 contrast agents. In this study, we present tumor vasculature-targeted imaging in mice using Mn3O4 NPs through conjugation to the anti-CD105 antibody TRC105 and radionuclide copper-64 (64Cu, t1/2: 12.7 h). The Mn3O4 conjugated NPs, 64Cu-NOTA-Mn3O4@PEG-TRC105, exhibited sufficient stability in vitro and in vivo. Serial positron emission tomography (PET) and magnetic resonance imaging (MRI) studies evaluated the pharmacokinetics and demonstrated targeting of 64Cu-NOTA-Mn3O4@PEG-TRC105 to 4T1 murine breast tumors in vivo, compared to 64Cu-NOTA-Mn3O4@PEG. The specificity of 64Cu-NOTA-Mn3O4@PEG-TRC105 for the vascular marker CD105 was confirmed through in vivo, in vitro, and ex vivo experiments. Since Mn3O4 conjugated NPs exhibited desirable properties for T1 enhanced imaging and low toxicity, the tumor-specific Mn3O4 conjugated NPs reported in this study may serve as promising multifunctional nanoplatforms for precise cancer imaging and diagnosis.
KW - cancer
KW - CD105 (endoglin)
KW - magnetic resonance imaging (MRI)
KW - manganese oxide nanoparticles
KW - positron emission tomography (PET)
UR - http://www.scopus.com/inward/record.url?scp=85033499169&partnerID=8YFLogxK
U2 - 10.1021/acsami.7b12216
DO - 10.1021/acsami.7b12216
M3 - Journal article
C2 - 29028311
AN - SCOPUS:85033499169
SN - 1944-8244
VL - 9
SP - 38304
EP - 38312
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 44
ER -
