A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography

Nan Li,1,2,* Zilin Yu,1,* Truc Thuy Pham,1,* Philip J Blower,1 Ran Yan1 1Division of Imaging Sciences and Biomedical Engineering, St Thomas’ Hospital, King’s College London, London, UK; 2Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmac...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Li N, Yu Z, Pham TT, Blower PJ, Yan R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	liposome zirconium-89 PET pharmacokinetics Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c30bb8532db24e16869794ba1263d21f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c30bb8532db24e16869794ba1263d21f
record_format	dspace
spelling	oai:doaj.org-article:c30bb8532db24e16869794ba1263d21f2021-12-02T04:23:12ZA generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography1178-2013https://doaj.org/article/c30bb8532db24e16869794ba1263d21f2017-04-01T00:00:00Zhttps://www.dovepress.com/a-generic-89zr-labeling-method-to-quantify-the-in-vivo-pharmacokinetic-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Nan Li,1,2,* Zilin Yu,1,* Truc Thuy Pham,1,* Philip J Blower,1 Ran Yan1 1Division of Imaging Sciences and Biomedical Engineering, St Thomas’ Hospital, King’s College London, London, UK; 2Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Liposomal nanoparticles are versatile drug delivery vehicles that show great promise in cancer therapy. In an effort to quantitatively measure their in vivo pharmacokinetics, we developed a highly efficient 89Zr liposome-labeling method based on a rapid ligand exchange reaction between the membrane-permeable 89Zr(8-hydroxyquinolinate)4 complex and the hydrophilic liposomal cavity-encapsulated deferoxamine (DFO). This novel 89Zr-labeling strategy allowed us to prepare radiolabeled forms of a folic acid (FA)-decorated active targeting 89Zr-FA-DFO-liposome, a thermosensitive 89Zr-DFO-liposome, and a renal avid 89Zr-PEG-DFO-liposome at room temperature with near-quantitative isolated radiochemical yields of 98%±1% (n=6), 98%±2% (n=5), and 97%±1% (n=3), respectively. These 89Zr-labeled liposomal nanoparticles showed remarkable stability in phosphate-buffered saline and serum at 37°C without leakage of radioactivity for 48 h. The uptake of 89Zr-FA-DFO-liposome by the folate receptor-overexpressing KB cells was almost 15-fold higher than the 89Zr-DFO-liposome in vitro. Positron emission tomography imaging and ex vivo biodistribution studies enabled us to observe the heterogeneous distribution of the 89Zr-FA-DFO-liposome and 89Zr-DFO-liposome in the KB tumor xenografts, the extensive kidney accumulation of the 89Zr-FA-DFO-liposome and 89Zr-PEG-DFO-liposome, and the different metabolic fate of the free and liposome-encapsulated 89Zr-DFO. It also unveiled the poor resistance of all three liposomes against endothelial uptake resulting in their catabolism and high uptake of free 89Zr in the skeleton. Thus, this technically simple 89Zr-labeling method would find widespread use to guide the development and clinical applications of novel liposomal nanomedicines. Keywords: liposome, zirconium-89, PET, pharmacokineticsLi NYu ZPham TTBlower PJYan RDove Medical Pressarticleliposomezirconium-89PETpharmacokineticsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3281-3294 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	liposome zirconium-89 PET pharmacokinetics Medicine (General) R5-920
spellingShingle	liposome zirconium-89 PET pharmacokinetics Medicine (General) R5-920 Li N Yu Z Pham TT Blower PJ Yan R A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography
description	Nan Li,1,2,* Zilin Yu,1,* Truc Thuy Pham,1,* Philip J Blower,1 Ran Yan1 1Division of Imaging Sciences and Biomedical Engineering, St Thomas’ Hospital, King’s College London, London, UK; 2Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Liposomal nanoparticles are versatile drug delivery vehicles that show great promise in cancer therapy. In an effort to quantitatively measure their in vivo pharmacokinetics, we developed a highly efficient 89Zr liposome-labeling method based on a rapid ligand exchange reaction between the membrane-permeable 89Zr(8-hydroxyquinolinate)4 complex and the hydrophilic liposomal cavity-encapsulated deferoxamine (DFO). This novel 89Zr-labeling strategy allowed us to prepare radiolabeled forms of a folic acid (FA)-decorated active targeting 89Zr-FA-DFO-liposome, a thermosensitive 89Zr-DFO-liposome, and a renal avid 89Zr-PEG-DFO-liposome at room temperature with near-quantitative isolated radiochemical yields of 98%±1% (n=6), 98%±2% (n=5), and 97%±1% (n=3), respectively. These 89Zr-labeled liposomal nanoparticles showed remarkable stability in phosphate-buffered saline and serum at 37°C without leakage of radioactivity for 48 h. The uptake of 89Zr-FA-DFO-liposome by the folate receptor-overexpressing KB cells was almost 15-fold higher than the 89Zr-DFO-liposome in vitro. Positron emission tomography imaging and ex vivo biodistribution studies enabled us to observe the heterogeneous distribution of the 89Zr-FA-DFO-liposome and 89Zr-DFO-liposome in the KB tumor xenografts, the extensive kidney accumulation of the 89Zr-FA-DFO-liposome and 89Zr-PEG-DFO-liposome, and the different metabolic fate of the free and liposome-encapsulated 89Zr-DFO. It also unveiled the poor resistance of all three liposomes against endothelial uptake resulting in their catabolism and high uptake of free 89Zr in the skeleton. Thus, this technically simple 89Zr-labeling method would find widespread use to guide the development and clinical applications of novel liposomal nanomedicines. Keywords: liposome, zirconium-89, PET, pharmacokinetics
format	article
author	Li N Yu Z Pham TT Blower PJ Yan R
author_facet	Li N Yu Z Pham TT Blower PJ Yan R
author_sort	Li N
title	A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography
title_short	A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography
title_full	A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography
title_fullStr	A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography
title_full_unstemmed	A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography
title_sort	generic 89zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/c30bb8532db24e16869794ba1263d21f
work_keys_str_mv	AT lin ageneric89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT yuz ageneric89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT phamtt ageneric89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT blowerpj ageneric89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT yanr ageneric89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT lin generic89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT yuz generic89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT phamtt generic89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT blowerpj generic89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography AT yanr generic89zrlabelingmethodtoquantifytheinvivopharmacokineticsofliposomalnanoparticleswithpositronemissiontomography
_version_	1718401271766974464

A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography

Ejemplares similares