Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor Imaging

Labeling of RGD peptides with near-infrared fluorophores yields optical probes for noninvasive imaging of tumors overexpressing α v β 3 integrins. An important prerequisite for optimum detection sensitivity in vivo is strongly absorbing and highly emissive probes with a known fluorescence lifetime....

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Main Authors: Julia Eva Mathejczyk, Jutta Pauli, Christian Dullin, Joanna Napp, Lutz-F. Tietze, Horst Kessler, Ute Resch-Genger, Frauke Alves
Format: Article
Language:English
Published: SAGE Publishing 2011-11-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2011.00018
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author Julia Eva Mathejczyk
Jutta Pauli
Christian Dullin
Joanna Napp
Lutz-F. Tietze
Horst Kessler
Ute Resch-Genger
Frauke Alves
author_facet Julia Eva Mathejczyk
Jutta Pauli
Christian Dullin
Joanna Napp
Lutz-F. Tietze
Horst Kessler
Ute Resch-Genger
Frauke Alves
author_sort Julia Eva Mathejczyk
collection DOAJ
description Labeling of RGD peptides with near-infrared fluorophores yields optical probes for noninvasive imaging of tumors overexpressing α v β 3 integrins. An important prerequisite for optimum detection sensitivity in vivo is strongly absorbing and highly emissive probes with a known fluorescence lifetime. The RGD-Cy5.5 optical probe was derived by coupling Cy5.5 to a cyclic arginine–glycine–aspartic acid– d -phenylalanine–lysine (RGDfK) peptide via an aminohexanoic acid spacer. Spectroscopic properties of the probe were studied in different matrices in comparison to Cy5.5. For in vivo imaging, human glioblastoma cells were subcutaneously implanted into nude mice, and in vivo fluorescence intensity and lifetime were measured. The fluorescence quantum yield and lifetime of Cy5.5 were found to be barely affected on RGD conjugation but dramatically changed in the presence of proteins. By time domain fluorescence imaging, we demonstrated specific binding of RGD-Cy5.5 to glioblastoma xenografts in nude mice. Discrimination of unspecific fluorescence by lifetime-gated analysis further enhanced the detection sensitivity of RGD-Cy5.5-derived signals. We characterized RGD-Cy5.5 as a strongly emissive and stable probe adequate for selective targeting of α v β 3 integrins. The specificity and thus the overall detection sensitivity in vivo were optimized with lifetime gating, based on the previous determination of the probes fluorescence lifetime under application-relevant conditions.
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spelling doaj-art-34267dc446c04b92be0b8bfb01923cef2025-01-02T22:39:33ZengSAGE PublishingMolecular Imaging1536-01212011-11-011010.2310/7290.2011.0001810.2310_7290.2011.00018Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor ImagingJulia Eva MathejczykJutta PauliChristian DullinJoanna NappLutz-F. TietzeHorst KesslerUte Resch-GengerFrauke AlvesLabeling of RGD peptides with near-infrared fluorophores yields optical probes for noninvasive imaging of tumors overexpressing α v β 3 integrins. An important prerequisite for optimum detection sensitivity in vivo is strongly absorbing and highly emissive probes with a known fluorescence lifetime. The RGD-Cy5.5 optical probe was derived by coupling Cy5.5 to a cyclic arginine–glycine–aspartic acid– d -phenylalanine–lysine (RGDfK) peptide via an aminohexanoic acid spacer. Spectroscopic properties of the probe were studied in different matrices in comparison to Cy5.5. For in vivo imaging, human glioblastoma cells were subcutaneously implanted into nude mice, and in vivo fluorescence intensity and lifetime were measured. The fluorescence quantum yield and lifetime of Cy5.5 were found to be barely affected on RGD conjugation but dramatically changed in the presence of proteins. By time domain fluorescence imaging, we demonstrated specific binding of RGD-Cy5.5 to glioblastoma xenografts in nude mice. Discrimination of unspecific fluorescence by lifetime-gated analysis further enhanced the detection sensitivity of RGD-Cy5.5-derived signals. We characterized RGD-Cy5.5 as a strongly emissive and stable probe adequate for selective targeting of α v β 3 integrins. The specificity and thus the overall detection sensitivity in vivo were optimized with lifetime gating, based on the previous determination of the probes fluorescence lifetime under application-relevant conditions.https://doi.org/10.2310/7290.2011.00018
spellingShingle Julia Eva Mathejczyk
Jutta Pauli
Christian Dullin
Joanna Napp
Lutz-F. Tietze
Horst Kessler
Ute Resch-Genger
Frauke Alves
Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor Imaging
Molecular Imaging
title Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor Imaging
title_full Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor Imaging
title_fullStr Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor Imaging
title_full_unstemmed Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor Imaging
title_short Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor Imaging
title_sort spectroscopically well characterized rgd optical probe as a prerequisite for lifetime gated tumor imaging
url https://doi.org/10.2310/7290.2011.00018
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