Multiplexed in vivo fluorescence optical imaging of the therapeutic efficacy of photodynamic therapy

Abstract In our study we wanted to elucidate a time frame for in vivo optical imaging of the therapeutic efficacy of photodynamic therapy (PDT) by using a multiplexed imaging approach for detecting apoptosis and vascularization. The internalization of the photosensitizer Foslip® into tongue-squamous...

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Bibliographic Details
Published in:Biomaterials 2013-12, Vol.34 (38), p.10075-10083
Main Authors: Haedicke, Katja, Gräfe, Susanna, Lehmann, Frank, Hilger, Ingrid
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Annexin A5 - metabolism
Annexin V
Apoptosis
Apoptosis - genetics
Apoptosis - physiology
Cell Line, Tumor
Dentistry
Female
Fluorescence optical imaging
Mice
Microscopy, Fluorescence
Multiplexed imaging
Photochemotherapy - methods
Tumor vascularization
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Summary:Abstract In our study we wanted to elucidate a time frame for in vivo optical imaging of the therapeutic efficacy of photodynamic therapy (PDT) by using a multiplexed imaging approach for detecting apoptosis and vascularization. The internalization of the photosensitizer Foslip® into tongue-squamous epithelium carcinoma cells (CAL-27) was examined in vitro and in vivo. For detecting apoptosis, annexin V was covalently coupled to the near-infrared dye DY-734 and the spectroscopic properties and binding affinity to apoptotic CAL-27 cells were elucidated. CAL-27 tumor bearing mice were treated with PDT and injected 2 days and 2 weeks thereafter with DY-734-annexin V. PDT-induced changes in tumor vascularization were detected with the contrast agent IRDye® 800CW RGD up to 3 weeks after PDT. A perinuclear enrichment of Foslip® could be seen in vitro which was reflected in an accumulation in CAL-27 tumors in vivo. The DY-734-annexin V (coupling efficiency 30–50%) revealed a high binding affinity to apoptotic compared to non-apoptotic cells (17.2% vs. 1.2%) with a K D -value of 20 n m . After PDT-treatment, the probe showed a significantly higher ( p
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.08.087