Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography

Rongzuo Xu1, Todd Lyle Kaneshiro1, Eun-Kee Jeong2, Dennis L Parker2, Zheng-Rong Lu31Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; 2Department of Radiology, University of Utah, Salt Lake City, UT, USA; 3Department of Biomedical Engineering, Cas...

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Autores principales:	Rongzuo Xu, Todd Lyle Kaneshiro, Eun-Kee Jeong, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2bcb2d0a5b8341eabaa4fef00ae31d36
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spelling	oai:doaj.org-article:2bcb2d0a5b8341eabaa4fef00ae31d362021-12-02T07:28:33ZSynthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography1176-91141178-2013https://doaj.org/article/2bcb2d0a5b8341eabaa4fef00ae31d362010-09-01T00:00:00Zhttp://www.dovepress.com/synthesis-and-evaluation-of-nanoglobule-cystamine-gd-do3a-a-biodegrada-a5324https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Rongzuo Xu1, Todd Lyle Kaneshiro1, Eun-Kee Jeong2, Dennis L Parker2, Zheng-Rong Lu31Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; 2Department of Radiology, University of Utah, Salt Lake City, UT, USA; 3Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USAAbstract: Dynamic contrast-enhanced magnetic resonance imaging has been recently shown to be effective for diagnostic urography. High-resolution urographic images can be acquired with T1 contrast agents for the kidney and urinary tract with minimal noise in the abdomen. Currently, clinical contrast agents are low molecular weight agents and can rapidly extravasate from blood circulation, leading to slow contrast agent elimination through kidney and consequently providing limited contrast enhancement in urinary tract. In this study, a new biodegradable macromolecular contrast agent, nanoglobule-G4-cystamine-(Gd-DO3A), was prepared by conjugating Gd-DO3A chelates on the surface of a generation 4 nanoglobule, poly-l-lysine octa(3-aminopropyl)silsesquioxane dendrimer, via a disulfide spacer, where the carrier had a precisely defined nanosize that is far smaller than the renal filtration threshold. The in vivo contrast enhancement and dynamic imaging of the urinary tract of the agent was evaluated in nude mice using a low molecular weight agent Gd(DTPA-BMA) as a control. The agent eliminated rapidly from blood circulation and accumulated more abundantly in urinary tract than Gd(DTPA-BMA). The fast elimination kinetics is ideal for functional evaluation of the kidneys. The morphology of the kidneys and urinary tract was better visualized by the biodegradable nanoglobular contrast agent than Gd(DTPA-BMA). The agent also resulted in low liver contrast enhancement, indicating low nonspecific tissue deposition. These features render the G4 nanoglobule-cystamine-(Gd-DO3A) conjugate a promising contrast agent for magnetic resonance urography.Keywords: dendrimer, gadolinium(III) contrast agent, disulfide bond, nanoparticle Rongzuo XuTodd Lyle KaneshiroEun-Kee Jeonget alDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2010, Iss default, Pp 707-713 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Rongzuo Xu Todd Lyle Kaneshiro Eun-Kee Jeong et al Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography
description	Rongzuo Xu1, Todd Lyle Kaneshiro1, Eun-Kee Jeong2, Dennis L Parker2, Zheng-Rong Lu31Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; 2Department of Radiology, University of Utah, Salt Lake City, UT, USA; 3Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USAAbstract: Dynamic contrast-enhanced magnetic resonance imaging has been recently shown to be effective for diagnostic urography. High-resolution urographic images can be acquired with T1 contrast agents for the kidney and urinary tract with minimal noise in the abdomen. Currently, clinical contrast agents are low molecular weight agents and can rapidly extravasate from blood circulation, leading to slow contrast agent elimination through kidney and consequently providing limited contrast enhancement in urinary tract. In this study, a new biodegradable macromolecular contrast agent, nanoglobule-G4-cystamine-(Gd-DO3A), was prepared by conjugating Gd-DO3A chelates on the surface of a generation 4 nanoglobule, poly-l-lysine octa(3-aminopropyl)silsesquioxane dendrimer, via a disulfide spacer, where the carrier had a precisely defined nanosize that is far smaller than the renal filtration threshold. The in vivo contrast enhancement and dynamic imaging of the urinary tract of the agent was evaluated in nude mice using a low molecular weight agent Gd(DTPA-BMA) as a control. The agent eliminated rapidly from blood circulation and accumulated more abundantly in urinary tract than Gd(DTPA-BMA). The fast elimination kinetics is ideal for functional evaluation of the kidneys. The morphology of the kidneys and urinary tract was better visualized by the biodegradable nanoglobular contrast agent than Gd(DTPA-BMA). The agent also resulted in low liver contrast enhancement, indicating low nonspecific tissue deposition. These features render the G4 nanoglobule-cystamine-(Gd-DO3A) conjugate a promising contrast agent for magnetic resonance urography.Keywords: dendrimer, gadolinium(III) contrast agent, disulfide bond, nanoparticle
format	article
author	Rongzuo Xu Todd Lyle Kaneshiro Eun-Kee Jeong et al
author_facet	Rongzuo Xu Todd Lyle Kaneshiro Eun-Kee Jeong et al
author_sort	Rongzuo Xu
title	Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography
title_short	Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography
title_full	Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography
title_fullStr	Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography
title_full_unstemmed	Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography
title_sort	synthesis and evaluation of nanoglobule-cystamine-(gd-do3a), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/2bcb2d0a5b8341eabaa4fef00ae31d36
work_keys_str_mv	AT rongzuoxu synthesisandevaluationofnanoglobulecystaminegddo3aabiodegradablenanosizedmagneticresonancecontrastagentfordynamiccontrastenhancedmagneticresonanceurography AT toddlylekaneshiro synthesisandevaluationofnanoglobulecystaminegddo3aabiodegradablenanosizedmagneticresonancecontrastagentfordynamiccontrastenhancedmagneticresonanceurography AT eunkeejeong synthesisandevaluationofnanoglobulecystaminegddo3aabiodegradablenanosizedmagneticresonancecontrastagentfordynamiccontrastenhancedmagneticresonanceurography AT etal synthesisandevaluationofnanoglobulecystaminegddo3aabiodegradablenanosizedmagneticresonancecontrastagentfordynamiccontrastenhancedmagneticresonanceurography
_version_	1718399390275600384

Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography

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