Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain
Name
elife-70237-v1.pdf
Description
Published version
Size
2.74 MB
Format
Adobe PDF
Checksum (MD5)
47424a24e5adfa00cdc46b74def5060b
Author(s)
Desai, Mitul
Sharma, Jitendra
Slusarczyk, Adrian L
Chapin, Ashley A
Ohlendorf, Robert
Wisniowska, Agata
Sur, Mriganka
Jasanoff, Alan
Date Issued
2021
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Desai, Mitul, Sharma, Jitendra, Slusarczyk, Adrian L, Chapin, Ashley A, Ohlendorf, Robert et al. 2021. "Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain." eLife, 10.
Version
Final published version
Abstract
Molecular imaging could have great utility for detecting, classifying, and guiding treatment of brain disorders, but existing probes offer limited capability for assessing relevant physiological parameters. Here, we describe a potent approach for noninvasive mapping of cancer-associated enzyme activity using a molecular sensor that acts on the vasculature, providing a diagnostic readout via local changes in hemodynamic image contrast. The sensor is targeted at the fibroblast activation protein (FAP), an extracellular dipeptidase and clinically relevant biomarker of brain tumor biology. Optimal FAP sensor variants were identified by screening a series of prototypes for responsiveness in a cell-based bioassay. The best variant was then applied for quantitative neuroimaging of FAP activity in rats, where it reveals nanomolar-scale FAP expression by xenografted cells. The activated probe also induces robust hemodynamic contrast in nonhuman primate brain. This work thus demonstrates a potentially translatable strategy for ultrasensitive functional imaging of molecular targets in neuromedicine.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/ELIFE.70237
