Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1785033340648161280 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10141219 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT huynhphuongtu gadoliniumcyclic14710tetraazacyclododecane14710tetraaceticacidclicksulfonylfluorideforprobingserineproteaseactivityinmagneticresonanceimaging AT vuhuyduc gadoliniumcyclic14710tetraazacyclododecane14710tetraaceticacidclicksulfonylfluorideforprobingserineproteaseactivityinmagneticresonanceimaging AT ryujunghwa gadoliniumcyclic14710tetraazacyclododecane14710tetraaceticacidclicksulfonylfluorideforprobingserineproteaseactivityinmagneticresonanceimaging AT kimheesu gadoliniumcyclic14710tetraazacyclododecane14710tetraaceticacidclicksulfonylfluorideforprobingserineproteaseactivityinmagneticresonanceimaging AT junghoesu gadoliniumcyclic14710tetraazacyclododecane14710tetraaceticacidclicksulfonylfluorideforprobingserineproteaseactivityinmagneticresonanceimaging AT younsungwon gadoliniumcyclic14710tetraazacyclododecane14710tetraaceticacidclicksulfonylfluorideforprobingserineproteaseactivityinmagneticresonanceimaging |