7T MRI and molecular studies of Dotarem (gadoterate meglumine) retention in macrophages.
Gadolinium-based MRI contrast agent Dotarem is commonly used in the clinic. Free Gd3+ is very toxic. Because the crystallographic radius of Gd3+ and Ca2+ is very similar, Gd3+ can compete with Ca2+ in the regulations of cellular functions. Gadolinium is retained in organs and tissues, but the effect...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Journal of Magnetic Resonance Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666441022000553 |
| _version_ | 1811294171976171520 |
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| author | Ahmed Uosef Arijita Subuddhi Annie Lu Henry V. Ubelaker Christof Karmonik Jarek Wosik Rafik M. Ghobrial Malgorzata Kloc |
| author_facet | Ahmed Uosef Arijita Subuddhi Annie Lu Henry V. Ubelaker Christof Karmonik Jarek Wosik Rafik M. Ghobrial Malgorzata Kloc |
| author_sort | Ahmed Uosef |
| collection | DOAJ |
| description | Gadolinium-based MRI contrast agent Dotarem is commonly used in the clinic. Free Gd3+ is very toxic. Because the crystallographic radius of Gd3+ and Ca2+ is very similar, Gd3+ can compete with Ca2+ in the regulations of cellular functions. Gadolinium is retained in organs and tissues, but the effects of gadolinium retention are mostly unknown. There is also no information how gadolinium retention impacts immune cells and signaling pathways regulated by Ca2+ such as RhoA/mTORC1 and mTORC2, which control various, including actin cytoskeleton-dependent, cellular functions. We developed the 7T MRI-based method to analyze gadolinium-based MRI contrast agent retention in isolated immune cells (macrophages) and study the effects of gadolinium retention on the expression of RhoA, mTORC1, mTORC2, and mitochondria, Golgi, and ER markers. We showed that macrophages retain gadolinium for at least seven days after exposure. Gadolinium retention downregulated the expression of RhoA, mTORC1 component Raptor and mTORC2 component Rictor proteins, and dysregulated the expression level of organelle markers. The method described here can be used for monitoring gadolinium levels and effects in isolated cells, such as the immune cells in the blood of patients exposed to contrast-enhanced MRI. |
| first_indexed | 2024-04-13T05:12:32Z |
| format | Article |
| id | doaj.art-132a4f1e0d9e46dfaadd38988576dc94 |
| institution | Directory Open Access Journal |
| issn | 2666-4410 |
| language | English |
| last_indexed | 2024-04-13T05:12:32Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Magnetic Resonance Open |
| spelling | doaj.art-132a4f1e0d9e46dfaadd38988576dc942022-12-22T03:00:59ZengElsevierJournal of Magnetic Resonance Open2666-44102022-12-01121000857T MRI and molecular studies of Dotarem (gadoterate meglumine) retention in macrophages.Ahmed Uosef0Arijita Subuddhi1Annie Lu2Henry V. Ubelaker3Christof Karmonik4Jarek Wosik5Rafik M. Ghobrial6Malgorzata Kloc7The Houston Methodist Research Institute, Transplant Immunology, Houston, TX, USA;; The Houston Methodist Hospital, Department of Surgery, Houston, TX, USA;The Houston Methodist Research Institute, Transplant Immunology, Houston, TX, USA;; The Houston Methodist Hospital, Department of Surgery, Houston, TX, USA;The Houston Methodist Research Institute, Transplant Immunology, Houston, TX, USA;; The Houston Methodist Hospital, Department of Surgery, Houston, TX, USA;The Houston Methodist Research Institute, Transplant Immunology, Houston, TX, USA;; The Houston Methodist Hospital, Department of Surgery, Houston, TX, USA;Translational Imaging Center, Houston Methodist Research Institute, Houston, TX, USA;Electrical and Computer Engineering Department, University of Houston, Houston, Texas 77204, USA;; Texas Center for Superconductivity, University of Houston, Houston, Texas 77204, USA;The Houston Methodist Research Institute, Transplant Immunology, Houston, TX, USA;; The Houston Methodist Hospital, Department of Surgery, Houston, TX, USA;The Houston Methodist Research Institute, Transplant Immunology, Houston, TX, USA;; The Houston Methodist Hospital, Department of Surgery, Houston, TX, USA;; The University of Texas, MD Anderson Cancer Center, Department of Genetics, Houston, TX, USA.; Corresponding author.Gadolinium-based MRI contrast agent Dotarem is commonly used in the clinic. Free Gd3+ is very toxic. Because the crystallographic radius of Gd3+ and Ca2+ is very similar, Gd3+ can compete with Ca2+ in the regulations of cellular functions. Gadolinium is retained in organs and tissues, but the effects of gadolinium retention are mostly unknown. There is also no information how gadolinium retention impacts immune cells and signaling pathways regulated by Ca2+ such as RhoA/mTORC1 and mTORC2, which control various, including actin cytoskeleton-dependent, cellular functions. We developed the 7T MRI-based method to analyze gadolinium-based MRI contrast agent retention in isolated immune cells (macrophages) and study the effects of gadolinium retention on the expression of RhoA, mTORC1, mTORC2, and mitochondria, Golgi, and ER markers. We showed that macrophages retain gadolinium for at least seven days after exposure. Gadolinium retention downregulated the expression of RhoA, mTORC1 component Raptor and mTORC2 component Rictor proteins, and dysregulated the expression level of organelle markers. The method described here can be used for monitoring gadolinium levels and effects in isolated cells, such as the immune cells in the blood of patients exposed to contrast-enhanced MRI.http://www.sciencedirect.com/science/article/pii/S2666441022000553Magnetic resonance imaging7T MRIDotaremGadoliniumRetentionMacrophage |
| spellingShingle | Ahmed Uosef Arijita Subuddhi Annie Lu Henry V. Ubelaker Christof Karmonik Jarek Wosik Rafik M. Ghobrial Malgorzata Kloc 7T MRI and molecular studies of Dotarem (gadoterate meglumine) retention in macrophages. Journal of Magnetic Resonance Open Magnetic resonance imaging 7T MRI Dotarem Gadolinium Retention Macrophage |
| title | 7T MRI and molecular studies of Dotarem (gadoterate meglumine) retention in macrophages. |
| title_full | 7T MRI and molecular studies of Dotarem (gadoterate meglumine) retention in macrophages. |
| title_fullStr | 7T MRI and molecular studies of Dotarem (gadoterate meglumine) retention in macrophages. |
| title_full_unstemmed | 7T MRI and molecular studies of Dotarem (gadoterate meglumine) retention in macrophages. |
| title_short | 7T MRI and molecular studies of Dotarem (gadoterate meglumine) retention in macrophages. |
| title_sort | 7t mri and molecular studies of dotarem gadoterate meglumine retention in macrophages |
| topic | Magnetic resonance imaging 7T MRI Dotarem Gadolinium Retention Macrophage |
| url | http://www.sciencedirect.com/science/article/pii/S2666441022000553 |
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