Abstract
Purpose
The development of NIRF cathepsin activity probes offered the ability to visualize tumor associated tumor reaction and act as a surrogate marker to delineate the dysplastic lesions. One major type is a NIRF substrate of cathepsins (SBP), which is involved in catalytic way to produce high levels of fluorescence emission. The other major type (ABP) reacts with active cathepsins in stoichiometric manner since they bind covalently with their active center. Little is known about the sensitivity and the specificity of the NIRF probes to detect autochthonous developed dysplastic lesions. Dual laser NIRF endoscope provides a good tool to determine the efficiency of various NIRF probes in vivo in the same lesions.
Experimental design
In the current study, we validated both types of NIRF probes by using the dual laser NIRF endoscope to detect lesions colon cancer mouse model (TS4Cre/cAPC +/lox).
Results
The dual laser NIRF endoscope is emitting equal power with both lasers. It can detect with the same efficiency in 680 mode, as well as, 750 mode when NIFR probes of the same scaffold in vivo. When SBP and ABP were used, our results showed both probes are efficient enough to detect large polyps but small dysplastic lesions could not efficiently imaged with the ABP.
Conclusions
The dual laser NIRF endoscope is a powerful tool to validate probes. The probes that react catalytically with the active center of cathepsins are more efficient than the ones that react stoichiometrically in detecting small lesions.
Document Type
Article
Publication Date
11-2-2018
Digital Object Identifier (DOI)
https://doi.org/10.1371/journal.pone.0206568
Funding Information
Authors (TAB and EG) received a grant from Northwestern memorial Foundation (excellence in Academic Medicine: 222) for 3 years.
Related Content
All relevant data are within the paper and its Supporting Information files.
S1 Fig. Specifications of the fiberscopes that could be used with the two-laser excitation light source. https://doi.org/10.1371/journal.pone.0206568.s001 (TIF)
Repository Citation
Shrivastav, Manisha; Gounaris, Elias; Khan, Mohammad W.; Ko, Jeffrey; Ryu, Stacy H.; Bogyo, Matthew; Larson, Andrew; Barrett, Terrence A.; and Bentrem, David J., "Validation of Near Infrared Fluorescence (NIRF) Probes In Vivo with Dual Laser NIRF Endoscope" (2018). Internal Medicine Faculty Publications. 163.
https://uknowledge.uky.edu/internalmedicine_facpub/163
S1 Fig. Specifications of the fiberscopes that could be used with the two-laser excitation light source.
Notes/Citation Information
Published in PLOS ONE, v. 13, no. 11, e0206568, p. 1-14.
© 2018 Shrivastav et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
A correction to this article can be found at: https://doi.org/10.1371/journal.pone.0210677