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Using High Content Imaging to Quantify Target Engagement in Adherent Cells
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A microCT-based platform to quantify drug targeting.

Brandon J Ausk1, Adam N Tucker2, Philippe Huber2

  • 1In Situ Therapeutic Solutions Inc, Seattle, USA. brandon.ausk@istherasol.com.

European Radiology Experimental
|August 2, 2023
PubMed
Summary
This summary is machine-generated.

Distributed dosing of botulinum toxin type A (BTxA) significantly improves soft-tissue drug coverage compared to single-bolus injections. This microcomputed tomography (microCT) imaging platform enables precise quantification for optimizing heterotopic ossification prophylaxis.

Keywords:
Drug delivery systemsOrthopedicsOssification (heterotopic)RabbitsX-ray microtomography

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Area of Science:

  • Biomedical Engineering
  • Musculoskeletal Research
  • Pharmacology

Background:

  • Heterotopic ossification (HO) is a common complication following musculoskeletal trauma and surgery.
  • Accurate distribution of prophylactic treatments, such as botulinum toxin type A (BTxA), is crucial for effective HO inhibition.
  • Current methods lack precise quantification of drug distribution in soft tissues.

Purpose of the Study:

  • To develop and validate a high-resolution imaging strategy for assessing drug distribution in soft tissues.
  • To compare the efficacy of distributed dosing versus single-bolus injection for drug delivery.
  • To overcome barriers in the clinical translation of BTxA for HO prophylaxis.

Main Methods:

  • Utilized microcomputed tomography (microCT) with an iodine-containing contrast agent to image drug distribution in rabbit muscle.
  • Developed a 3D-printed soft-tissue holder to facilitate controlled injections.
  • Quantified drug coverage within a defined volume of interest (VOI) based on proximity to injected fluid.

Main Results:

  • The microCT approach enabled high-resolution quantification of injection distribution.
  • Distributed dosing via a prototype system achieved significantly greater VOI coverage (72%) compared to single-bolus injection (43%).
  • Distributed dosing also enhanced the precision of injection targeting.

Conclusions:

  • Microcomputed tomography (microCT) is a precise method for quantifying drug distribution in soft tissues.
  • Distributed dosing strategies are essential for maximizing drug coverage in targeted soft-tissue volumes.
  • The developed imaging platform facilitates rapid optimization of injection parameters for clinical devices aimed at HO prevention.