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- Title
MMP-2/9-Specific Activatable Lifetime Imaging Agent.
- Authors
Rood, Marcus T. M.; Raspe, Marcel; ten Hove, Jan Bart; Jalink, Kees; Velders, Aldrik H.; van Leeuwen, Fijs W. B.
- Abstract
Optical (molecular) imaging can benefit from a combination of the high signal-to-background ratio of activatable fluorescence imaging with the high specificity of luminescence lifetime imaging. To allow for this combination, both imaging techniques were integrated in a single imaging agent, a so-called activatable lifetime imaging agent. Important in the design of this imaging agent is the use of two luminophores that are tethered by a specific peptide with a hairpin-motive that ensured close proximity of the two while also having a specific amino acid sequence available for enzymatic cleavage by tumor-related MMP-2/9. Ir(ppy)³ and Cy5 were used because in close proximity the emission intensities of both luminophores were quenched and the influence of Cy5 shortens the Ir(ppy)³ luminescence lifetime from 98 ns to 30 ns. Upon cleavage in vitro, both effects are undone, yielding an increase in Ir(ppy)³ and Cy5 luminescence and a restoration of Ir(ppy)³ luminescence lifetime to 94 ns. As a reference for the luminescence activation, a similar imaging agent with the more common Cy3-Cy5 fluorophore pair was used. Our findings underline that the combination of enzymatic signal activation with lifetime imaging is possible and that it provides a promising method in the design of future disease specific imaging agents.
- Subjects
OPTICAL imaging sensors; IMAGE sensors; AMINO acid sequence; LUMINOPHORES; LUMINESCENCE
- Publication
Sensors (14248220), 2015, Vol 15, Issue 5, p11076
- ISSN
1424-8220
- Publication type
Article
- DOI
10.3390/s150511076