Necrosis avid near infrared fluorescent cyanines for imaging cell death and their use to monitor therapeutic efficacy in mouse tumor models
Xie B, Stammes MA, Van Driel PBAA, Cruz LJ, Knol-Blankevoort VT, Lowik MAM, Mezzanotte L, Que I, Chan A, Van Den Wijngaard JPHM, Siebes M, Gottschalk S, Razansky D, Ntziachristos V, Keereweer S, Horobin RW, Hoehn M, Kaijzel EL, Van Beek ER, Snoeks TJA, Lowik CWGM (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 6
Pages Range: 39036-39049
Journal Issue: 36
Abstract
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.
Involved external institutions
Leiden University
Netherlands (NL)
Percuros B.V.
Netherlands (NL)
University of Amsterdam
Netherlands (NL)
Technische Universität München (TUM)
Germany (DE)
University of Glasgow
United Kingdom (GB)
Netherlands (NL)
Percuros B.V.
Netherlands (NL)
University of Amsterdam
Netherlands (NL)
Technische Universität München (TUM)
Germany (DE)
University of Glasgow
United Kingdom (GB)
How to cite
APA:
Xie, B., Stammes, M.A., Van Driel, P.B.A.A., Cruz, L.J., Knol-Blankevoort, V.T., Lowik, M.A.M.,... Lowik, C.W.G.M. (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), 39036-39049. https://doi.org/10.18632/oncotarget.5498
MLA:
Xie, Bangwen, et al. "Necrosis avid near infrared fluorescent cyanines for imaging cell death and their use to monitor therapeutic efficacy in mouse tumor models." Oncotarget 6.36 (2015): 39036-39049.
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