Chelator-Free Labeling of Layered Double Hydroxide Nanoparticles for in Vivo PET Imaging

Sixiang Shi; Brianne C. Fliss; Zi Gu; Yian Zhu; Hao Hong; Hector F. Valdovinos; Reinier Hernandez; Shreya Goel; Haiming Luo; Feng Chen; Todd E. Barnhart; Robert J. Nickles; Zhi Ping Xu; Weibo Cai

doi:10.1038/srep16930

Chelator-Free Labeling of Layered Double Hydroxide Nanoparticles for in Vivo PET Imaging

Sixiang Shi, Brianne C. Fliss, Zi Gu, Yian Zhu, Hao Hong, Hector F. Valdovinos, Reinier Hernandez, Shreya Goel, Haiming Luo, Feng Chen, Todd E. Barnhart, Robert J. Nickles, Zhi Ping Xu, Weibo Cai

Research output: Journal article publication › Journal article › Academic research › peer-review

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Abstract

Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64 Cu²⁺ and trivalent cation 44 Sc³⁺ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89 Zr⁴⁺ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64 Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.

Original language	English
Article number	16930
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep16930
Publication status	Published - 20 Nov 2015
Externally published	Yes

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title = "Chelator-Free Labeling of Layered Double Hydroxide Nanoparticles for in Vivo PET Imaging",

abstract = "Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64 Cu2+ and trivalent cation 44 Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89 Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64 Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.",

author = "Sixiang Shi and Fliss, {Brianne C.} and Zi Gu and Yian Zhu and Hao Hong and Valdovinos, {Hector F.} and Reinier Hernandez and Shreya Goel and Haiming Luo and Feng Chen and Barnhart, {Todd E.} and Nickles, {Robert J.} and Xu, {Zhi Ping} and Weibo Cai",

note = "Funding Information: This work is supported, in part, by the University of Wisconsin-Madison, the National Institutes of Health (NIBIB/NCI 1R01CA169365, P30CA014520 and 5T32GM08349), the Department of Defense (W81XWH-11-1-0644), the National Science Foundation (DGE-1256259), the American Cancer Society (125246-RSG-13-099-01-CCE), ARC Future Fellowship (FT120100813) and Wisconsin Distinguished Graduate Fellowship. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.",

year = "2015",

month = nov,

day = "20",

doi = "10.1038/srep16930",

language = "English",

volume = "5",

journal = "Scientific Reports",

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T1 - Chelator-Free Labeling of Layered Double Hydroxide Nanoparticles for in Vivo PET Imaging

AU - Shi, Sixiang

AU - Fliss, Brianne C.

AU - Gu, Zi

AU - Zhu, Yian

AU - Hong, Hao

AU - Valdovinos, Hector F.

AU - Hernandez, Reinier

AU - Goel, Shreya

AU - Luo, Haiming

AU - Chen, Feng

AU - Barnhart, Todd E.

AU - Nickles, Robert J.

AU - Xu, Zhi Ping

AU - Cai, Weibo

N1 - Funding Information: This work is supported, in part, by the University of Wisconsin-Madison, the National Institutes of Health (NIBIB/NCI 1R01CA169365, P30CA014520 and 5T32GM08349), the Department of Defense (W81XWH-11-1-0644), the National Science Foundation (DGE-1256259), the American Cancer Society (125246-RSG-13-099-01-CCE), ARC Future Fellowship (FT120100813) and Wisconsin Distinguished Graduate Fellowship. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.

PY - 2015/11/20

Y1 - 2015/11/20

N2 - Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64 Cu2+ and trivalent cation 44 Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89 Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64 Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.

AB - Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64 Cu2+ and trivalent cation 44 Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89 Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64 Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.

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Chelator-Free Labeling of Layered Double Hydroxide Nanoparticles for in Vivo PET Imaging

Abstract

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