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Designed Ankyrin Repeat Proteins as Novel Binders for Ultrasound Molecular Imaging

Kosareva, Alexandra; Punjabi, Mukesh; Ochoa-Espinosa, Amanda; Xu, Lifen; Schaefer, Jonas V; Dreier, Birgit; Plückthun, Andreas; Kaufmann, Beat A (2021). Designed Ankyrin Repeat Proteins as Novel Binders for Ultrasound Molecular Imaging. Ultrasound in Medicine & Biology, 47(9):2664-2675.

Abstract

Clinical translation of ultrasound molecular imaging will depend on the development of binders that can easily be generated, manufactured and coupled, and that are compatible with in vivo use. We describe targeted microbubbles (MBs) using designed ankyrin repeat proteins (DARPins) as a novel class of such translatable binders. Candidate DARPin binders for vascular cell adhesion molecule 1, an endothelial cell adhesion molecule involved in inflammatory processes, were selected using ribosome display and coupled to MBs. Flow-chamber assays of five MBs carrying high-affinity binders showed selective retention on endothelial cells activated by tumor necrosis factor-α for two binders compared with a MB carrying a control DARPin. In vivo ultrasound molecular imaging in a murine hind-limb inflammation model demonstrated up to a fourfold signal enhancement for three of the five MBs versus control. However, there was no correlation between results from flow-chamber assays and in vivo imaging. Thus, we conclude that ultrasound molecular imaging of inflammation using DARPin binders is feasible per se, but that screening of candidates cannot be accomplished with flow-chamber assays as used in our study.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Radiological and Ultrasound Technology
Life Sciences > Biophysics
Physical Sciences > Acoustics and Ultrasonics
Language:English
Date:September 2021
Deposited On:07 Dec 2021 09:28
Last Modified:26 Oct 2024 01:39
Publisher:Elsevier
ISSN:0301-5629
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.ultrasmedbio.2021.04.027
PubMed ID:34144832

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