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Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging

Serine protease is linked to a wide range of diseases, prompting the development of robust, selective, and sensitive protease assays and sensing methods. However, the clinical needs for serine protease activity imaging have not yet been met, and the efficient in vivo detection and imaging of serine...

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Autores principales: Huynh, Phuong Tu, Vu, Huy Duc, Ryu, Junghwa, Kim, Hee Su, Jung, Hoesu, Youn, Sung Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141219/
https://www.ncbi.nlm.nih.gov/pubmed/37110769
http://dx.doi.org/10.3390/molecules28083538
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author Huynh, Phuong Tu
Vu, Huy Duc
Ryu, Junghwa
Kim, Hee Su
Jung, Hoesu
Youn, Sung Won
author_facet Huynh, Phuong Tu
Vu, Huy Duc
Ryu, Junghwa
Kim, Hee Su
Jung, Hoesu
Youn, Sung Won
author_sort Huynh, Phuong Tu
collection PubMed
description Serine protease is linked to a wide range of diseases, prompting the development of robust, selective, and sensitive protease assays and sensing methods. However, the clinical needs for serine protease activity imaging have not yet been met, and the efficient in vivo detection and imaging of serine protease remain challenging. Here, we report the development of the gadolinium-cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-click-Sulfonyl Fluoride (Gd-DOTA-click-SF) MRI contrast agent targeting serine protease. The HR-FAB mass spectrum confirmed the successful formation of our designed chelate. The molar longitudinal relaxivity (r(1)) of the Gd-DOTA-click-SF probe (r(1) = 6.82 mM(−1) s(−1)) was significantly higher than that of Dotarem (r(1) = 4.63 mM(−1) s(−1)), in the range of 0.01–0.64 mM at 9.4 T. The in vitro cellular study and the transmetallation kinetics study showed that the safety and stability of this probe are comparable to those of conventional Dotarem. Ex vivo abdominal aortic aneurysm (AAA) MRI revealed that this probe has a contrast-agent-to-noise ratio (CNR) that is approximately 51 ± 23 times greater than that of Dotarem. This study of superior visualization of AAA suggests that it has the potential to detect elastase in vivo and supports the feasibility of probing serine protease activity in T1-weighted MRI.
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spelling pubmed-101412192023-04-29 Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging Huynh, Phuong Tu Vu, Huy Duc Ryu, Junghwa Kim, Hee Su Jung, Hoesu Youn, Sung Won Molecules Article Serine protease is linked to a wide range of diseases, prompting the development of robust, selective, and sensitive protease assays and sensing methods. However, the clinical needs for serine protease activity imaging have not yet been met, and the efficient in vivo detection and imaging of serine protease remain challenging. Here, we report the development of the gadolinium-cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-click-Sulfonyl Fluoride (Gd-DOTA-click-SF) MRI contrast agent targeting serine protease. The HR-FAB mass spectrum confirmed the successful formation of our designed chelate. The molar longitudinal relaxivity (r(1)) of the Gd-DOTA-click-SF probe (r(1) = 6.82 mM(−1) s(−1)) was significantly higher than that of Dotarem (r(1) = 4.63 mM(−1) s(−1)), in the range of 0.01–0.64 mM at 9.4 T. The in vitro cellular study and the transmetallation kinetics study showed that the safety and stability of this probe are comparable to those of conventional Dotarem. Ex vivo abdominal aortic aneurysm (AAA) MRI revealed that this probe has a contrast-agent-to-noise ratio (CNR) that is approximately 51 ± 23 times greater than that of Dotarem. This study of superior visualization of AAA suggests that it has the potential to detect elastase in vivo and supports the feasibility of probing serine protease activity in T1-weighted MRI. MDPI 2023-04-17 /pmc/articles/PMC10141219/ /pubmed/37110769 http://dx.doi.org/10.3390/molecules28083538 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huynh, Phuong Tu
Vu, Huy Duc
Ryu, Junghwa
Kim, Hee Su
Jung, Hoesu
Youn, Sung Won
Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging
title Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging
title_full Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging
title_fullStr Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging
title_full_unstemmed Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging
title_short Gadolinium-Cyclic 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid-Click-Sulfonyl Fluoride for Probing Serine Protease Activity in Magnetic Resonance Imaging
title_sort gadolinium-cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-click-sulfonyl fluoride for probing serine protease activity in magnetic resonance imaging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141219/
https://www.ncbi.nlm.nih.gov/pubmed/37110769
http://dx.doi.org/10.3390/molecules28083538
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