RT Journal Article
SR Electronic
T1 Target-responsive vasoactive probes for ultrasensitive molecular imaging
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 786079
DO 10.1101/786079
A1 Robert Ohlendorf
A1 Agata Wiśniowska
A1 Mitul Desai
A1 Ali Barandov
A1 Adrian L. Slusarczyk
A1 Alan Jasanoff
YR 2019
UL http://biorxiv.org/content/early/2019/10/03/786079.abstract
AB 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.