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2 March 2018 Long-term fluorescence lifetime imaging of a genetically encoded sensor for caspase-3 activity in mouse tumor xenografts
Victoria V. Zherdeva, Natalia I. Kazachkina, Vladislav I. Shcheslavskiy, Alexander P. Savitsky
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Journal of Biomedical Optics, Vol. 23, Issue 3, 035002 (March 2018). https://doi.org/10.1117/1.JBO.23.3.035002
Abstract
Caspase-3 is known for its role in apoptosis and programmed cell death regulation. We detected caspase-3 activation in vivo in tumor xenografts via shift of mean fluorescence lifetimes of a caspase-3 sensor. We used the genetically encoded sensor TR23K based on the red fluorescent protein TagRFP and chromoprotein KFP linked by 23 amino acid residues (TagRFP-23-KFP) containing a specific caspase cleavage DEVD motif to monitor the activity of caspase-3 in tumor xenografts by means of fluorescence lifetime imaging-Forster resonance energy transfer. Apoptosis was induced by injection of paclitaxel for A549 lung adenocarcinoma and etoposide and cisplatin for HEp-2 pharynx adenocarcinoma. We observed a shift in lifetime distribution from 1.6 to 1.9 ns to 2.1 to 2.4 ns, which indicated the activation of caspase-3. Even within the same tumor, the lifetime varied presumably due to the tumor heterogeneity and the different depth of tumor invasion. Thus, processing time-resolved fluorescence images allows detection of both the cleaved and noncleaved states of the TR23K sensor in real-time mode during the course of several weeks noninvasively. This approach can be used in drug screening, facilitating the development of new anticancer agents as well as improvement of chemotherapy efficiency and its adaptation for personal treatment.
CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
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Victoria V. Zherdeva, Natalia I. Kazachkina, Vladislav I. Shcheslavskiy, and Alexander P. Savitsky "Long-term fluorescence lifetime imaging of a genetically encoded sensor for caspase-3 activity in mouse tumor xenografts," Journal of Biomedical Optics 23(3), 035002 (2 March 2018). https://doi.org/10.1117/1.JBO.23.3.035002
Received: 25 October 2017; Accepted: 1 February 2018; Published: 2 March 2018
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Cited by 13 scholarly publications.
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KEYWORDS
Tumors
Luminescence
Sensors
Fluorescence lifetime imaging
In vivo imaging
Picosecond phenomena
Cell death
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