[<sup>18</sup>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...
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2021
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oai:doaj.org-article:8725d3f997024c7cada22894fcce82522021-11-25T18:40:22Z[<sup>18</sup>F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound10.3390/pharmaceutics131117521999-4923https://doaj.org/article/8725d3f997024c7cada22894fcce82522021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1752https://doaj.org/toc/1999-4923Focused 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 [<sup>18</sup>F]2-fluoro-2-deoxy-sorbitol ([<sup>18</sup>F]FDS) was evaluated as a small-molecule (paracellular) marker of blood-brain barrier (BBB) integrity. [<sup>18</sup>F]FDS was straightforwardly produced from chemical reduction of commercial [<sup>18</sup>F]2-deoxy-2-fluoro-D-glucose. [<sup>18</sup>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 (<i>n</i> = 5; <i>p</i> < 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 [<sup>18</sup>F]FDS by 2.4 ± 0.8-fold (<i>V</i><sub>T</sub>; <i>p</i> < 0.01). Low variability (=10.1%) of <i>V</i><sub>T</sub> values in the sonicated hemisphere suggests reproducibility of the estimation of BBB permeability and FUS method. [<sup>18</sup>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.Gaëlle HugonSébastien GoutalAmbre DaubaLouise BreuilBenoit LarratAlexandra WinkelerAnthony NovellNicolas TournierMDPI AGarticleblood-brain barrierintegrity markersorbitolpositron emission tomographyfocused ultrasoundPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1752, p 1752 (2021) |
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blood-brain barrier integrity marker sorbitol positron emission tomography focused ultrasound Pharmacy and materia medica RS1-441 |
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blood-brain barrier integrity marker sorbitol positron emission tomography focused ultrasound Pharmacy and materia medica RS1-441 Gaëlle Hugon Sébastien Goutal Ambre Dauba Louise Breuil Benoit Larrat Alexandra Winkeler Anthony Novell Nicolas Tournier [<sup>18</sup>F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
| 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 [<sup>18</sup>F]2-fluoro-2-deoxy-sorbitol ([<sup>18</sup>F]FDS) was evaluated as a small-molecule (paracellular) marker of blood-brain barrier (BBB) integrity. [<sup>18</sup>F]FDS was straightforwardly produced from chemical reduction of commercial [<sup>18</sup>F]2-deoxy-2-fluoro-D-glucose. [<sup>18</sup>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 (<i>n</i> = 5; <i>p</i> < 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 [<sup>18</sup>F]FDS by 2.4 ± 0.8-fold (<i>V</i><sub>T</sub>; <i>p</i> < 0.01). Low variability (=10.1%) of <i>V</i><sub>T</sub> values in the sonicated hemisphere suggests reproducibility of the estimation of BBB permeability and FUS method. [<sup>18</sup>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 |
article |
| author |
Gaëlle Hugon Sébastien Goutal Ambre Dauba Louise Breuil Benoit Larrat Alexandra Winkeler Anthony Novell Nicolas Tournier |
| author_facet |
Gaëlle Hugon Sébastien Goutal Ambre Dauba Louise Breuil Benoit Larrat Alexandra Winkeler Anthony Novell Nicolas Tournier |
| author_sort |
Gaëlle Hugon |
| title |
[<sup>18</sup>F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
| title_short |
[<sup>18</sup>F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
| title_full |
[<sup>18</sup>F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
| title_fullStr |
[<sup>18</sup>F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
| title_full_unstemmed |
[<sup>18</sup>F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound |
| title_sort |
[<sup>18</sup>f]2-fluoro-2-deoxy-sorbitol pet imaging for quantitative monitoring of enhanced blood-brain barrier permeability induced by focused ultrasound |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/8725d3f997024c7cada22894fcce8252 |
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