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[(18)F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound
Focused ultrasound in combination with microbubbles (FUS) provides an effective means to locally enhance the delivery of therapeutics to the brain. Translational and quantitative imaging techniques are needed to noninvasively monitor and optimize the impact of FUS on blood-brain barrier (BBB) permea...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621256/ https://www.ncbi.nlm.nih.gov/pubmed/34834167 http://dx.doi.org/10.3390/pharmaceutics13111752 |
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author | Hugon, Gaëlle Goutal, Sébastien Dauba, Ambre Breuil, Louise Larrat, Benoit Winkeler, Alexandra Novell, Anthony Tournier, Nicolas |
author_facet | Hugon, Gaëlle Goutal, Sébastien Dauba, Ambre Breuil, Louise Larrat, Benoit Winkeler, Alexandra Novell, Anthony Tournier, Nicolas |
author_sort | Hugon, Gaëlle |
collection | PubMed |
description | Focused ultrasound in combination with microbubbles (FUS) provides an effective means to locally enhance the delivery of therapeutics to the brain. Translational and quantitative imaging techniques are needed to noninvasively monitor and optimize the impact of FUS on blood-brain barrier (BBB) permeability in vivo. Positron-emission tomography (PET) imaging using [(18)F]2-fluoro-2-deoxy-sorbitol ([(18)F]FDS) was evaluated as a small-molecule (paracellular) marker of blood-brain barrier (BBB) integrity. [(18)F]FDS was straightforwardly produced from chemical reduction of commercial [(18)F]2-deoxy-2-fluoro-D-glucose. [(18)F]FDS and the invasive BBB integrity marker Evan’s blue (EB) were i.v. injected in mice after an optimized FUS protocol designed to generate controlled hemispheric BBB disruption. Quantitative determination of the impact of FUS on the BBB permeability was determined using kinetic modeling. A 2.2 ± 0.5-fold higher PET signal (n = 5; p < 0.01) was obtained in the sonicated hemisphere and colocalized with EB staining observed post mortem. FUS significantly increased the blood-to-brain distribution of [(18)F]FDS by 2.4 ± 0.8-fold (V(T); p < 0.01). Low variability (=10.1%) of V(T) values in the sonicated hemisphere suggests reproducibility of the estimation of BBB permeability and FUS method. [(18)F]FDS PET provides a readily available, sensitive and reproducible marker of BBB permeability to noninvasively monitor the extent of BBB disruption induced by FUS in vivo. |
format | Online Article Text |
id | pubmed-8621256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86212562021-11-27 [(18)F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound Hugon, Gaëlle Goutal, Sébastien Dauba, Ambre Breuil, Louise Larrat, Benoit Winkeler, Alexandra Novell, Anthony Tournier, Nicolas Pharmaceutics Article Focused ultrasound in combination with microbubbles (FUS) provides an effective means to locally enhance the delivery of therapeutics to the brain. Translational and quantitative imaging techniques are needed to noninvasively monitor and optimize the impact of FUS on blood-brain barrier (BBB) permeability in vivo. Positron-emission tomography (PET) imaging using [(18)F]2-fluoro-2-deoxy-sorbitol ([(18)F]FDS) was evaluated as a small-molecule (paracellular) marker of blood-brain barrier (BBB) integrity. [(18)F]FDS was straightforwardly produced from chemical reduction of commercial [(18)F]2-deoxy-2-fluoro-D-glucose. [(18)F]FDS and the invasive BBB integrity marker Evan’s blue (EB) were i.v. injected in mice after an optimized FUS protocol designed to generate controlled hemispheric BBB disruption. Quantitative determination of the impact of FUS on the BBB permeability was determined using kinetic modeling. A 2.2 ± 0.5-fold higher PET signal (n = 5; p < 0.01) was obtained in the sonicated hemisphere and colocalized with EB staining observed post mortem. FUS significantly increased the blood-to-brain distribution of [(18)F]FDS by 2.4 ± 0.8-fold (V(T); p < 0.01). Low variability (=10.1%) of V(T) values in the sonicated hemisphere suggests reproducibility of the estimation of BBB permeability and FUS method. [(18)F]FDS PET provides a readily available, sensitive and reproducible marker of BBB permeability to noninvasively monitor the extent of BBB disruption induced by FUS in vivo. MDPI 2021-10-20 /pmc/articles/PMC8621256/ /pubmed/34834167 http://dx.doi.org/10.3390/pharmaceutics13111752 Text en © 2021 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 Hugon, Gaëlle Goutal, Sébastien Dauba, Ambre Breuil, Louise Larrat, Benoit Winkeler, Alexandra Novell, Anthony Tournier, Nicolas [(18)F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
title | [(18)F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
title_full | [(18)F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
title_fullStr | [(18)F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
title_full_unstemmed | [(18)F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
title_short | [(18)F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
title_sort | [(18)f]2-fluoro-2-deoxy-sorbitol pet imaging for quantitative monitoring of enhanced blood-brain barrier permeability induced by focused ultrasound |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621256/ https://www.ncbi.nlm.nih.gov/pubmed/34834167 http://dx.doi.org/10.3390/pharmaceutics13111752 |
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