Development of 64Cu-loaded Perfluoropentane Nanodroplet: A Potential Tumor Theragnostic Nano-carrier and Dual-Modality PET-Ultrasound Imaging Agents

Unchol Shin; Jungyoung Kim; Jiwoong Lee; Donghee Park; Changmoon Lee; Hyon Chel Jung; Jiae Park; Kyochul Lee; Min Woo Lee; Suhng Wook Kim; Jongbum Seo

doi:10.1016/j.ultrasmedbio.2020.05.019

Development of ⁶⁴Cu-loaded Perfluoropentane Nanodroplet: A Potential Tumor Theragnostic Nano-carrier and Dual-Modality PET-Ultrasound Imaging Agents

Unchol Shin, Jungyoung Kim, Jiwoong Lee, Donghee Park, Changmoon Lee, Hyon Chel Jung, Jiae Park, Kyochul Lee, Min Woo Lee, Suhng Wook Kim, Jongbum Seo

School of Health and Environmental Science

Research output: Contribution to journal › Article › peer-review

Abstract

The purpose of this study was to develop and preliminarily evaluate phospholipid-shelled nanodroplets (NDs) encapsulating perfluoropentane (PFP) and radioactive ⁶⁴Cu as a hybrid positron emission tomography (PET)-ultrasound (US) probe. PFP NDs were fabricated by mixing liquid-phase PFP with a phospholipid solution. The ⁶⁴Cu was encapsulated into the NDs in a size-controlled manner by exploiting the hydrophobicity of ⁶⁴Cu-diacetyl-bis(N⁴-methylthiosemicarbazone) (⁶⁴Cu-ATSM) using a vial mixer and an extruder. The fabricated ⁶⁴Cu-loaded PFP NDs (⁶⁴Cu-PFP NDs) were evaluated using in vitro/in vivo PET-computed tomography (PET-CT), US imaging and transmission electron microscopy. In the in vitro PET images, the ⁶⁴Cu-PFP NDs were observed as a hot spot in the lower section of the test tube. In the acquired US images, the mean region of interest brightness values of ⁶⁴Cu-PFP NDs were revealed by their strong echo image. In a tumor-bearing mouse animal model, tumor uptake of the ⁶⁴Cu-PFP NDs was low, that is, approximately 65%, compared with that of only free ⁶⁴Cu, as determined by PET-delayed imaging analysis. The dual-function concept of the NDs is expected to contribute to the prognosis and effectiveness of therapy by fusing the science and technology of nuclear medicine and US.

Original language	English
Pages (from-to)	2775-2784
Number of pages	10
Journal	Ultrasound in Medicine and Biology
Volume	46
Issue number	10
DOIs	https://doi.org/10.1016/j.ultrasmedbio.2020.05.019
Publication status	Published - 2020 Oct

Keywords

Cu-ATSM
Nanodroplets
PET
Perfluoropentane
Phospholipid
Ultrasound

ASJC Scopus subject areas

Biophysics
Radiological and Ultrasound Technology
Acoustics and Ultrasonics

Access to Document

10.1016/j.ultrasmedbio.2020.05.019

Cite this

Shin, U., Kim, J., Lee, J., Park, D., Lee, C., Jung, H. C., Park, J., Lee, K., Lee, M. W., Kim, S. W., & Seo, J. (2020). Development of ⁶⁴Cu-loaded Perfluoropentane Nanodroplet: A Potential Tumor Theragnostic Nano-carrier and Dual-Modality PET-Ultrasound Imaging Agents. Ultrasound in Medicine and Biology, 46(10), 2775-2784. https://doi.org/10.1016/j.ultrasmedbio.2020.05.019

Development of ⁶⁴Cu-loaded Perfluoropentane Nanodroplet : A Potential Tumor Theragnostic Nano-carrier and Dual-Modality PET-Ultrasound Imaging Agents. / Shin, Unchol; Kim, Jungyoung; Lee, Jiwoong; Park, Donghee; Lee, Changmoon; Jung, Hyon Chel; Park, Jiae; Lee, Kyochul; Lee, Min Woo; Kim, Suhng Wook; Seo, Jongbum.

In: Ultrasound in Medicine and Biology, Vol. 46, No. 10, 10.2020, p. 2775-2784.

Research output: Contribution to journal › Article › peer-review

Shin, U, Kim, J, Lee, J, Park, D, Lee, C, Jung, HC, Park, J, Lee, K, Lee, MW, Kim, SW & Seo, J 2020, 'Development of ⁶⁴Cu-loaded Perfluoropentane Nanodroplet: A Potential Tumor Theragnostic Nano-carrier and Dual-Modality PET-Ultrasound Imaging Agents', Ultrasound in Medicine and Biology, vol. 46, no. 10, pp. 2775-2784. https://doi.org/10.1016/j.ultrasmedbio.2020.05.019

Shin, Unchol ; Kim, Jungyoung ; Lee, Jiwoong ; Park, Donghee ; Lee, Changmoon ; Jung, Hyon Chel ; Park, Jiae ; Lee, Kyochul ; Lee, Min Woo ; Kim, Suhng Wook ; Seo, Jongbum. / Development of ⁶⁴Cu-loaded Perfluoropentane Nanodroplet : A Potential Tumor Theragnostic Nano-carrier and Dual-Modality PET-Ultrasound Imaging Agents. In: Ultrasound in Medicine and Biology. 2020 ; Vol. 46, No. 10. pp. 2775-2784.

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title = "Development of 64Cu-loaded Perfluoropentane Nanodroplet: A Potential Tumor Theragnostic Nano-carrier and Dual-Modality PET-Ultrasound Imaging Agents",

abstract = "The purpose of this study was to develop and preliminarily evaluate phospholipid-shelled nanodroplets (NDs) encapsulating perfluoropentane (PFP) and radioactive 64Cu as a hybrid positron emission tomography (PET)-ultrasound (US) probe. PFP NDs were fabricated by mixing liquid-phase PFP with a phospholipid solution. The 64Cu was encapsulated into the NDs in a size-controlled manner by exploiting the hydrophobicity of 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) using a vial mixer and an extruder. The fabricated 64Cu-loaded PFP NDs (64Cu-PFP NDs) were evaluated using in vitro/in vivo PET-computed tomography (PET-CT), US imaging and transmission electron microscopy. In the in vitro PET images, the 64Cu-PFP NDs were observed as a hot spot in the lower section of the test tube. In the acquired US images, the mean region of interest brightness values of 64Cu-PFP NDs were revealed by their strong echo image. In a tumor-bearing mouse animal model, tumor uptake of the 64Cu-PFP NDs was low, that is, approximately 65%, compared with that of only free 64Cu, as determined by PET-delayed imaging analysis. The dual-function concept of the NDs is expected to contribute to the prognosis and effectiveness of therapy by fusing the science and technology of nuclear medicine and US.",

keywords = "Cu-ATSM, Nanodroplets, PET, Perfluoropentane, Phospholipid, Ultrasound",

author = "Unchol Shin and Jungyoung Kim and Jiwoong Lee and Donghee Park and Changmoon Lee and Jung, {Hyon Chel} and Jiae Park and Kyochul Lee and Lee, {Min Woo} and Kim, {Suhng Wook} and Jongbum Seo",

note = "Funding Information: This work was supported by a Nuclear Research and Development Program of the National Research Foundation of Korea (NRF) grant funded by the Korean government (Nos. 2017 M2 A2 A6 A02019904 and 2020 R1 A2 C1008995). This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning (MSIP) (NRF-2014 M3 A6 A3063636) and a Korea University Grant. Publisher Copyright: {\textcopyright} 2020 World Federation for Ultrasound in Medicine & Biology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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AU - Shin, Unchol

AU - Kim, Jungyoung

AU - Lee, Jiwoong

AU - Park, Donghee

AU - Lee, Changmoon

AU - Jung, Hyon Chel

AU - Park, Jiae

AU - Lee, Kyochul

AU - Lee, Min Woo

AU - Kim, Suhng Wook

AU - Seo, Jongbum

N1 - Funding Information: This work was supported by a Nuclear Research and Development Program of the National Research Foundation of Korea (NRF) grant funded by the Korean government (Nos. 2017 M2 A2 A6 A02019904 and 2020 R1 A2 C1008995). This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning (MSIP) (NRF-2014 M3 A6 A3063636) and a Korea University Grant. Publisher Copyright: © 2020 World Federation for Ultrasound in Medicine & Biology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/10

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N2 - The purpose of this study was to develop and preliminarily evaluate phospholipid-shelled nanodroplets (NDs) encapsulating perfluoropentane (PFP) and radioactive 64Cu as a hybrid positron emission tomography (PET)-ultrasound (US) probe. PFP NDs were fabricated by mixing liquid-phase PFP with a phospholipid solution. The 64Cu was encapsulated into the NDs in a size-controlled manner by exploiting the hydrophobicity of 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) using a vial mixer and an extruder. The fabricated 64Cu-loaded PFP NDs (64Cu-PFP NDs) were evaluated using in vitro/in vivo PET-computed tomography (PET-CT), US imaging and transmission electron microscopy. In the in vitro PET images, the 64Cu-PFP NDs were observed as a hot spot in the lower section of the test tube. In the acquired US images, the mean region of interest brightness values of 64Cu-PFP NDs were revealed by their strong echo image. In a tumor-bearing mouse animal model, tumor uptake of the 64Cu-PFP NDs was low, that is, approximately 65%, compared with that of only free 64Cu, as determined by PET-delayed imaging analysis. The dual-function concept of the NDs is expected to contribute to the prognosis and effectiveness of therapy by fusing the science and technology of nuclear medicine and US.

AB - The purpose of this study was to develop and preliminarily evaluate phospholipid-shelled nanodroplets (NDs) encapsulating perfluoropentane (PFP) and radioactive 64Cu as a hybrid positron emission tomography (PET)-ultrasound (US) probe. PFP NDs were fabricated by mixing liquid-phase PFP with a phospholipid solution. The 64Cu was encapsulated into the NDs in a size-controlled manner by exploiting the hydrophobicity of 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) using a vial mixer and an extruder. The fabricated 64Cu-loaded PFP NDs (64Cu-PFP NDs) were evaluated using in vitro/in vivo PET-computed tomography (PET-CT), US imaging and transmission electron microscopy. In the in vitro PET images, the 64Cu-PFP NDs were observed as a hot spot in the lower section of the test tube. In the acquired US images, the mean region of interest brightness values of 64Cu-PFP NDs were revealed by their strong echo image. In a tumor-bearing mouse animal model, tumor uptake of the 64Cu-PFP NDs was low, that is, approximately 65%, compared with that of only free 64Cu, as determined by PET-delayed imaging analysis. The dual-function concept of the NDs is expected to contribute to the prognosis and effectiveness of therapy by fusing the science and technology of nuclear medicine and US.

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