A microCT-based platform to quantify drug targeting
Abstract 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-ti...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-08-01
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| Series: | European Radiology Experimental |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41747-023-00355-8 |
| _version_ | 1797752863094472704 |
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| author | Brandon J. Ausk Adam N. Tucker Philippe Huber Reza Firoozabadi Jeffrey M. Gross Ted S. Gross Steven D. Bain |
| author_facet | Brandon J. Ausk Adam N. Tucker Philippe Huber Reza Firoozabadi Jeffrey M. Gross Ted S. Gross Steven D. Bain |
| author_sort | Brandon J. Ausk |
| collection | DOAJ |
| description | Abstract 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-cm3-printed soft-tissue holder was developed. A centered 2-cm3 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 |
| first_indexed | 2024-03-12T17:10:39Z |
| format | Article |
| id | doaj.art-c990f9ed8ba04c4f93ede7ded4bd4a62 |
| institution | Directory Open Access Journal |
| issn | 2509-9280 |
| language | English |
| last_indexed | 2024-03-12T17:10:39Z |
| publishDate | 2023-08-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | European Radiology Experimental |
| spelling | doaj.art-c990f9ed8ba04c4f93ede7ded4bd4a622023-08-06T11:06:17ZengSpringerOpenEuropean Radiology Experimental2509-92802023-08-01711910.1186/s41747-023-00355-8A microCT-based platform to quantify drug targetingBrandon J. Ausk0Adam N. Tucker1Philippe Huber2Reza Firoozabadi3Jeffrey M. Gross4Ted S. Gross5Steven D. Bain6In Situ Therapeutic Solutions IncDepartment of Orthopaedics and Sports Medicine, University of WashingtonDepartment of Orthopaedics and Sports Medicine, University of WashingtonDepartment of Orthopaedics and Sports Medicine, University of WashingtonIn Situ Therapeutic Solutions IncDepartment of Orthopaedics and Sports Medicine, University of WashingtonDepartment of Orthopaedics and Sports Medicine, University of WashingtonAbstract 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-cm3-printed soft-tissue holder was developed. A centered 2-cm3 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 Abstracthttps://doi.org/10.1186/s41747-023-00355-8Drug delivery systemsOrthopedicsOssification (heterotopic)RabbitsX-ray microtomography |
| spellingShingle | Brandon J. Ausk Adam N. Tucker Philippe Huber Reza Firoozabadi Jeffrey M. Gross Ted S. Gross Steven D. Bain A microCT-based platform to quantify drug targeting European Radiology Experimental Drug delivery systems Orthopedics Ossification (heterotopic) Rabbits X-ray microtomography |
| 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 | Drug delivery systems Orthopedics Ossification (heterotopic) Rabbits X-ray microtomography |
| url | https://doi.org/10.1186/s41747-023-00355-8 |
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