Target-responsive vasoactive probes for ultrasensitive molecular imaging

• Published in: Nature communications Vol. 11; no. 1; pp. 2399 - 10
• Main Authors: Ohlendorf, Robert, Wiśniowska, Agata, Desai, Mitul, Barandov, Ali, Slusarczyk, Adrian L., Li, Nan, Jasanoff, Alan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.05.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 59/36; 59/57; 631/1647/245/2160; 631/61/338; 64/86; Animals; Appendages; Biomarkers; Biotin; Biotin - metabolism; Brain - diagnostic imaging; Brain - metabolism; Brain mapping; CHO Cells; Cricetinae; Cricetulus; Dopamine; Dopamine - metabolism; Functional magnetic resonance imaging; Heavy metal content; Heavy metals; HEK293 Cells; Hemodynamics; Humanities and Social Sciences; Humans; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Mapping; Medical imaging; Molecular Imaging - methods; Molecular Probes - chemistry; Molecular Probes - metabolism; multidisciplinary; Neuroimaging; Neurotransmitter Agents - metabolism; Neurotransmitters; Peptides; Peptides - metabolism; Pituitary Adenylate Cyclase-Activating Polypeptide - chemistry; Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism; Probes; Rats; Reproducibility of Results; Science; Science (multidisciplinary); Selectivity; Target detection; Vasoactive agents; Vasodilator Agents - chemistry; Vasodilator Agents - metabolism; Vasodilators
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16118-7

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. Noninvasive detection of molecular targets in living subjects could provide valuable insights into healthy function and disease. Here, the authors develop vasoactive imaging probes which allow wide-field in vivo mapping of nanomolar-level molecular species in rat brain.