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A microCT-based platform to quantify drug targeting
BACKGROUND: Heterotopic ossification (HO) is a frequent and debilitating complication of traumatic musculoskeletal injuries and orthopedic procedures. Prophylactic dosing of botulinum toxin type A (BTxA) holds potential as a novel treatment option if accurately distributed throughout soft-tissue vol...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Vienna
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397158/ https://www.ncbi.nlm.nih.gov/pubmed/37532922 http://dx.doi.org/10.1186/s41747-023-00355-8 |
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author | Ausk, Brandon J. Tucker, Adam N. Huber, Philippe Firoozabadi, Reza Gross, Jeffrey M. Gross, Ted S. Bain, Steven D. |
author_facet | Ausk, Brandon J. Tucker, Adam N. Huber, Philippe Firoozabadi, Reza Gross, Jeffrey M. Gross, Ted S. Bain, Steven D. |
author_sort | Ausk, Brandon J. |
collection | PubMed |
description | BACKGROUND: Heterotopic ossification (HO) is a frequent and debilitating complication of traumatic musculoskeletal injuries and orthopedic procedures. Prophylactic dosing of botulinum toxin type A (BTxA) holds potential as a novel treatment option if accurately distributed throughout soft-tissue volumes where protection is clinically desired. We developed a high-resolution, microcomputed tomography (microCT)-based imaging strategy to assess drug distribution and validated this platform by quantifying distribution achieved via a prototype delivery system versus a single-bolus injection. METHODS: We injected an iodine-containing contrast agent (iodixanol 320 mg I/mL) into dissected rabbit musculature followed by microCT imaging and analysis. To contrast the performance of distributed versus bolus injections, a three-dimensional (3D) 64-cm(3)-printed soft-tissue holder was developed. A centered 2-cm(3) volume of interest (VOI) was targeted with a single-bolus injection or an equal volume distributed injection delivered via a 3D-printed prototype. VOI drug coverage was quantified as a percentage of the VOI volume that was < 1.0 mm from the injected fluid. RESULTS: The microCT-based approach enabled high-resolution quantification of injection distribution within soft tissue. The distributed dosing prototype provided significantly greater tissue coverage of the targeted VOI (72 ± 3%, mean ± standard deviation) when compared to an equal volume bolus dose (43 ± 5%, p = 0.031) while also enhancing the precision of injection targeting. CONCLUSIONS: A microCT-based imaging technique precisely quantifies drug distribution within a soft-tissue VOI, providing a path to overcome a barrier for clinical translation of prophylactic inhibition of HO by BTxA. RELEVANCE STATEMENT: This platform will facilitate rapid optimization of injection parameters for clinical devices used to effectively and safely inhibit the formation of heterotopic ossification. KEY POINTS: • MicroCT provides high-resolution quantification of soft-tissue drug distribution. • Distributed dosing is required to maximize soft-tissue drug coverage. • Imaging platform will enable rapid screening of 3D-printed drug distribution prototypes. GRAPHICAL ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-10397158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Vienna |
record_format | MEDLINE/PubMed |
spelling | pubmed-103971582023-08-04 A microCT-based platform to quantify drug targeting Ausk, Brandon J. Tucker, Adam N. Huber, Philippe Firoozabadi, Reza Gross, Jeffrey M. Gross, Ted S. Bain, Steven D. Eur Radiol Exp Original Article BACKGROUND: Heterotopic ossification (HO) is a frequent and debilitating complication of traumatic musculoskeletal injuries and orthopedic procedures. Prophylactic dosing of botulinum toxin type A (BTxA) holds potential as a novel treatment option if accurately distributed throughout soft-tissue volumes where protection is clinically desired. We developed a high-resolution, microcomputed tomography (microCT)-based imaging strategy to assess drug distribution and validated this platform by quantifying distribution achieved via a prototype delivery system versus a single-bolus injection. METHODS: We injected an iodine-containing contrast agent (iodixanol 320 mg I/mL) into dissected rabbit musculature followed by microCT imaging and analysis. To contrast the performance of distributed versus bolus injections, a three-dimensional (3D) 64-cm(3)-printed soft-tissue holder was developed. A centered 2-cm(3) volume of interest (VOI) was targeted with a single-bolus injection or an equal volume distributed injection delivered via a 3D-printed prototype. VOI drug coverage was quantified as a percentage of the VOI volume that was < 1.0 mm from the injected fluid. RESULTS: The microCT-based approach enabled high-resolution quantification of injection distribution within soft tissue. The distributed dosing prototype provided significantly greater tissue coverage of the targeted VOI (72 ± 3%, mean ± standard deviation) when compared to an equal volume bolus dose (43 ± 5%, p = 0.031) while also enhancing the precision of injection targeting. CONCLUSIONS: A microCT-based imaging technique precisely quantifies drug distribution within a soft-tissue VOI, providing a path to overcome a barrier for clinical translation of prophylactic inhibition of HO by BTxA. RELEVANCE STATEMENT: This platform will facilitate rapid optimization of injection parameters for clinical devices used to effectively and safely inhibit the formation of heterotopic ossification. KEY POINTS: • MicroCT provides high-resolution quantification of soft-tissue drug distribution. • Distributed dosing is required to maximize soft-tissue drug coverage. • Imaging platform will enable rapid screening of 3D-printed drug distribution prototypes. GRAPHICAL ABSTRACT: [Image: see text] Springer Vienna 2023-08-03 /pmc/articles/PMC10397158/ /pubmed/37532922 http://dx.doi.org/10.1186/s41747-023-00355-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Ausk, Brandon J. Tucker, Adam N. Huber, Philippe Firoozabadi, Reza Gross, Jeffrey M. Gross, Ted S. Bain, Steven D. A microCT-based platform to quantify drug targeting |
title | A microCT-based platform to quantify drug targeting |
title_full | A microCT-based platform to quantify drug targeting |
title_fullStr | A microCT-based platform to quantify drug targeting |
title_full_unstemmed | A microCT-based platform to quantify drug targeting |
title_short | A microCT-based platform to quantify drug targeting |
title_sort | microct-based platform to quantify drug targeting |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397158/ https://www.ncbi.nlm.nih.gov/pubmed/37532922 http://dx.doi.org/10.1186/s41747-023-00355-8 |
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