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

Ultrasound Med Biol. 2020 Oct;46(10):2775-2784. doi: 10.1016/j.ultrasmedbio.2020.05.019. Epub 2020 Jul 9.

Authors

Affiliations

¹ Department of Biomedical Engineering, College of Health Sciences, Yonsei University, Seoul, Republic of Korea; College of Health Sciences, Institute of Health Science, Korea University, Seoul, Republic of Korea.
² Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
³ College of Health Sciences, Institute of Health Science, Korea University, Seoul, Republic of Korea.
⁴ Bioinfra Inc., Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁵ Department of Biomedical Engineering, College of Engineering, Chonnam National University, Gwangju, Republic of Korea.
⁶ Department of Biomedical Engineering, College of Health Sciences, Yonsei University, Seoul, Republic of Korea. Electronic address: jongbums@yonsei.ac.kr.

PMID: 32653208
DOI: 10.1016/j.ultrasmedbio.2020.05.019

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: (64)Cu-ATSM; Nanodroplets; PET; Perfluoropentane; Phospholipid; Ultrasound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Copper Radioisotopes*
Disease Models, Animal
Female
Fluorocarbons*
Mice
Mice, Inbred BALB C
Nanostructures*
Neoplasms / diagnostic imaging*
Neoplasms / therapy*
Positron-Emission Tomography / methods*
Ultrasonography

Substances

Copper Radioisotopes
Fluorocarbons
perfluoropentane