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Chemigenetic Far-Red Labels and Ca2+ Indicators Optimized for Photoacoustic Imaging
Alexander Cook1, Nikita Kaydanov1, Begoña Ugarte-Uribe1
1European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Journal of the American Chemical Society
|August 19, 2024
Summary
Researchers developed novel chemigenetic photoacoustic imaging reporters and calcium sensors. These advanced molecular tools enable deep tissue functional imaging and show superior performance in preclinical studies.
Area of Science:
- Biomedical Optics
- Molecular Imaging
- Biotechnology
Background:
- Photoacoustic imaging offers deep tissue visualization but lacks specific molecular reporters.
- Current limitations hinder the widespread adoption of photoacoustic imaging in biomedical applications like neuroimaging.
Purpose of the Study:
- To develop novel chemigenetic labels and calcium sensors for enhanced photoacoustic imaging.
- To engineer "acoustogenic" dyes and calcium indicators for targeted molecular reporting.
Main Methods:
- Rational design and engineering of far-red "acoustogenic" dyes.
- Integration of synthetic dyes with HaloTag-based self-labeling proteins.
- Development and testing of tunable calcium indicators.
Main Results:
- Engineered dyes exhibit high photoacoustic signal enhancement upon HaloTag binding.
- Developed reporters demonstrate superior signal intensity, sensitivity, and photostability in phantoms.
- Successfully applied probes for targeted neuronal labeling in mouse brain tissue and demonstrated in vivo application.
Conclusions:
- Established a new chemigenetic approach for designing photoacoustic reporters.
- The developed reporters facilitate deep tissue functional imaging.
- Paved the way for advanced applications of photoacoustic imaging in neuroscience and beyond.

