Necrosis avid near infrared fluorescent cyanines for imaging cell death and their use to monitor therapeutic efficacy in mouse tumor models

Xie, B. et al. (2015) Necrosis avid near infrared fluorescent cyanines for imaging cell death and their use to monitor therapeutic efficacy in mouse tumor models. Oncotarget, 6(36), pp. 39036-39049. (doi: 10.18632/oncotarget.5498) (PMID:26472022) (PMCID:PMC4770755)

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Quantification of tumor necrosis in cancer patients is of diagnostic value as the amount of necrosis is correlated with disease prognosis and it could also be used to predict early efficacy of anti-cancer treatments. In the present study, we identified two near infrared fluorescent (NIRF) carboxylated cyanines, HQ5 and IRDye 800CW (800CW), which possess strong necrosis avidity. In vitro studies showed that both dyes selectively bind to cytoplasmic proteins of dead cells that have lost membrane integrity. Affinity for cytoplasmic proteins was confirmed using quantitative structure activity relations modeling. In vivo results, using NIRF and optoacoustic imaging, confirmed the necrosis avid properties of HQ5 and 800CW in a mouse 4T1 breast cancer tumor model of spontaneous necrosis. Finally, in a mouse EL4 lymphoma tumor model, already 24 h post chemotherapy, a significant increase in 800CW fluorescence intensity was observed in treated compared to untreated tumors. In conclusion, we show, for the first time, that the NIRF carboxylated cyanines HQ5 and 800CW possess strong necrosis avid properties in vitro and in vivo. When translated to the clinic, these dyes may be used for diagnostic or prognostic purposes and for monitoring in vivo tumor response early after the start of treatment.

Item Type:Articles
Additional Information:This work was supported by project grants from TI Pharma (Project D4-603) and the EU Seventh Framework Programme: FP7-PEOPLE-2013-IAPP (612360 – BRAINPATH).
Glasgow Author(s) Enlighten ID:Horobin, Dr Richard
Authors: Xie, B., Stammes, M. A., van Driel, P. B.A.A., Cruz, L. J., Knol-Blankevoort, V. T., Löwik, M. A.M., Mezzanotte, L., Que, I., Chan, A., van den Wijngaard, J. P.H.M., Siebes, M., Gottschalk, S., Razansky, D., Ntziachristos, V., Keereweer, S., Horobin, R. W., Hoehn, M., Kaijzel, E. L., van Beek, E. R., Snoeks, T. J.A., and Löwik, C. W.G.M.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Oncotarget
Publisher:Impact Journals
ISSN (Online):1949-2553
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Oncotarget 6(36): 39036-39049
Publisher Policy:Reproduced under a Creative Commons License

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