Target-responsive vasoactive probes for ultrasensitive molecular imaging

Robert Ohlendorf, Agata Wiśniowska, Mitul Desai, Ali Barandov, Adrian L. Slusarczyk, Nan Li and Alan Jasanoff ()
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Robert Ohlendorf: Massachusetts Institute of Technology
Agata Wiśniowska: Massachusetts Institute of Technology
Mitul Desai: Massachusetts Institute of Technology
Ali Barandov: Massachusetts Institute of Technology
Adrian L. Slusarczyk: Massachusetts Institute of Technology
Nan Li: Massachusetts Institute of Technology
Alan Jasanoff: Massachusetts Institute of Technology

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract The ability to monitor molecules volumetrically throughout the body could provide valuable biomarkers for studies of healthy function and disease, but noninvasive detection of molecular targets in living subjects often suffers from poor sensitivity or selectivity. Here we describe a family of potent imaging probes that can be activated by molecules of interest in deep tissue, providing a basis for mapping nanomolar-scale analytes without the radiation or heavy metal content associated with traditional molecular imaging agents. The probes are reversibly caged vasodilators that induce responses detectable by hemodynamic imaging; they are constructed by combining vasoactive peptides with synthetic chemical appendages and protein blocking domains. We use this architecture to create ultrasensitive biotin-responsive imaging agents, which we apply for wide-field mapping of targets in rat brains using functional magnetic resonance imaging. We also adapt the sensor design for detecting the neurotransmitter dopamine, illustrating versatility of this approach for addressing biologically important molecules.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16118-7

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DOI: 10.1038/s41467-020-16118-7

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