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Necrosis avid near infrared fluorescent cyanines for imaging cell death and their use to monitor therapeutic efficacy in mouse tumor models.
- Source :
-
Oncotarget [Oncotarget] 2015 Nov 17; Vol. 6 (36), pp. 39036-49. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Antineoplastic Combined Chemotherapy Protocols pharmacology
Cell Death physiology
Cell Line, Tumor
Disease Models, Animal
Female
Humans
Lymphoma pathology
Mammary Neoplasms, Experimental pathology
Mice
Mice, Inbred BALB C
Mice, Nude
Microscopy, Confocal methods
Necrosis pathology
Quantitative Structure-Activity Relationship
Random Allocation
Carbocyanines chemistry
Fluorescent Dyes chemistry
Lymphoma diagnostic imaging
Lymphoma drug therapy
Mammary Neoplasms, Experimental diagnostic imaging
Mammary Neoplasms, Experimental drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 36
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26472022
- Full Text :
- https://doi.org/10.18632/oncotarget.5498