Target-responsive vasoactive probes for ultrasensitive molecular imaging

© 2020, The Author(s). 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 desc...

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Main Authors: Ohlendorf, Robert, Wiśniowska, Agata, Desai, Mitul, Barandov, Ali, Slusarczyk, Adrian L, Li, Nan, Jasanoff, Alan
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2021
Online Access:https://hdl.handle.net/1721.1/133097
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author Ohlendorf, Robert
Wiśniowska, Agata
Desai, Mitul
Barandov, Ali
Slusarczyk, Adrian L
Li, Nan
Jasanoff, Alan
author_facet Ohlendorf, Robert
Wiśniowska, Agata
Desai, Mitul
Barandov, Ali
Slusarczyk, Adrian L
Li, Nan
Jasanoff, Alan
author_sort Ohlendorf, Robert
collection MIT
description © 2020, The Author(s). 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.
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spelling mit-1721.1/1330972021-10-27T19:54:46Z Target-responsive vasoactive probes for ultrasensitive molecular imaging Ohlendorf, Robert Wiśniowska, Agata Desai, Mitul Barandov, Ali Slusarczyk, Adrian L Li, Nan Jasanoff, Alan © 2020, The Author(s). 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. 2021-10-25T17:45:56Z 2021-10-25T17:45:56Z 2020 2021-09-03T18:08:08Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133097 Ohlendorf, Robert, Wiśniowska, Agata, Desai, Mitul, Barandov, Ali, Slusarczyk, Adrian L et al. 2020. "Target-responsive vasoactive probes for ultrasensitive molecular imaging." Nature Communications, 11 (1). en 10.1038/S41467-020-16118-7 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature
spellingShingle Ohlendorf, Robert
Wiśniowska, Agata
Desai, Mitul
Barandov, Ali
Slusarczyk, Adrian L
Li, Nan
Jasanoff, Alan
Target-responsive vasoactive probes for ultrasensitive molecular imaging
title Target-responsive vasoactive probes for ultrasensitive molecular imaging
title_full Target-responsive vasoactive probes for ultrasensitive molecular imaging
title_fullStr Target-responsive vasoactive probes for ultrasensitive molecular imaging
title_full_unstemmed Target-responsive vasoactive probes for ultrasensitive molecular imaging
title_short Target-responsive vasoactive probes for ultrasensitive molecular imaging
title_sort target responsive vasoactive probes for ultrasensitive molecular imaging
url https://hdl.handle.net/1721.1/133097
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