MMP-2/9-Specific Activatable Lifetime Imaging Agent

Sensors

Marcus T.M. Rood²  Marcel Raspe¹  Jan Bart ten Hove²  Kees Jalink¹  Aldrik H. Velders²  Fijs W.B. van Leeuwen² 

[1] Division of Cell Biology I, Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands; E-Mails:;Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands; E-Mails:

关键词: iridium;    lifetime imaging;    luminescence;    enzymatic activation;    MMP;    FRET;    fluorescence;   

DOI  :  10.3390/s150511076

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.