Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain
| Autor: | Ashley A. Chapin, Robert Ohlendorf, Agata Wiśniowska, Jitendra Sharma, Alan Jasanoff, Mriganka Sur, Mitul Desai, Adrian L. Slusarczyk |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
QH301-705.5 brain Science Cell Brain tumor General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Fibroblast activation protein alpha Neuroimaging Endopeptidases Extracellular medicine Animals cancer Biology (General) Saimiri Cancer Biology General Immunology and Microbiology Brain Neoplasms business.industry General Neuroscience Membrane Proteins protease General Medicine medicine.disease molecular imaging saimiri sciureus Rats Biomarker (cell) Functional imaging medicine.anatomical_structure Rat Medicine Female Molecular imaging business Neuroscience Research Article MRI |
| Zdroj: | eLife, Vol 10 (2021) eLife |
| Popis: | 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 xeno-grafted 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. |
| Databáze: | OpenAIRE |
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