Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain [article]

MITUL M DESAI, Jitendra Sharma, Adrian L Slusarczyk, Ashley Chapin, Agata Wisniowska, Robert Ohlendorf, Mriganka Sur, Alan Jasanoff
2021 bioRxiv   pre-print
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
more » ... AP), 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 tumor cells. The activated probe also induces robust hemodynamic contrast in nonhuman primate brain. This work thus demonstrates a translatable strategy for ultrasensitive functional imaging of molecular targets in neuromedicine.
doi:10.1101/2021.05.11.443603 fatcat:jmcqsdmxqvaohkf2b6pd6v5d5q