Target-responsive vasoactive probes for ultrasensitive molecular imaging.
Animals
Biotin
/ metabolism
Brain
/ diagnostic imaging
CHO Cells
Cricetinae
Cricetulus
Dopamine
/ metabolism
HEK293 Cells
Humans
Magnetic Resonance Imaging
/ methods
Molecular Imaging
/ methods
Molecular Probes
/ chemistry
Neurotransmitter Agents
/ metabolism
Peptides
/ metabolism
Pituitary Adenylate Cyclase-Activating Polypeptide
/ chemistry
Rats
Reproducibility of Results
Vasodilator Agents
/ chemistry
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 05 2020
13 05 2020
Historique:
received:
14
08
2019
accepted:
03
04
2020
entrez:
15
5
2020
pubmed:
15
5
2020
medline:
11
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32404879
doi: 10.1038/s41467-020-16118-7
pii: 10.1038/s41467-020-16118-7
pmc: PMC7220906
doi:
Substances chimiques
Molecular Probes
0
Neurotransmitter Agents
0
Peptides
0
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Vasodilator Agents
0
Biotin
6SO6U10H04
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2399Subventions
Organisme : NINDS NIH HHS
ID : U01 NS103470
Pays : United States
Organisme : NINDS NIH HHS
ID : UF1 NS107712
Pays : United States
Organisme : NIDA NIH HHS
ID : R90 DA023427
Pays : United States
Organisme : NIMH NIH HHS
ID : R24 MH109081
Pays : United States
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