Clostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer

Identification of micrometastatic disease at the time of surgery remains extremely challenging in ovarian cancer patients. We used fluorescence microscopy, an in vivo imaging system and a fluorescence stereo microscope to evaluate fluorescence distribution in Claudin‐3‐ and ‐4‐overexpressing ovarian...

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Bibliographic Details
Published in:International journal of cancer 2015-12, Vol.137 (11), p.2618-2629
Main Authors: Cocco, Emiliano, Shapiro, Erik M., Gasparrini, Sara, Lopez, Salvatore, Schwab, Carlton L., Bellone, Stefania, Bortolomai, Ileana, Sumi, Natalia J., Bonazzoli, Elena, Nicoletti, Roberta, Deng, Yang, Saltzman, W. Mark, Zeiss, Caroline J., Centritto, Floriana, Black, Jonathan D., Silasi, Dan‐Arin, Ratner, Elena, Azodi, Masoud, Rutherford, Thomas J., Schwartz, Peter E., Pecorelli, Sergio, Santin, Alessandro D.
Format: Article
Language:English
Subjects:
Animals
Cancer
Chemotherapy
Claudin-3 - metabolism
Claudin-4 - metabolism
Clostridium perfringens
Clostridium perfringens enterotoxin
Drug resistance
Dyes
Enterotoxins - administration & dosage
Female
Fluorescent Dyes - administration & dosage
Humans
IRDye CW800
Medical research
Mice
Mice, SCID
Neoplasm Micrometastasis - pathology
Ovarian cancer
Ovarian Neoplasms - pathology
real‐time imaging
residual disease
Tumors
Xenograft Model Antitumor Assays - methods
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Summary:Identification of micrometastatic disease at the time of surgery remains extremely challenging in ovarian cancer patients. We used fluorescence microscopy, an in vivo imaging system and a fluorescence stereo microscope to evaluate fluorescence distribution in Claudin‐3‐ and ‐4‐overexpressing ovarian tumors, floating tumor clumps isolated from ascites and healthy organs. To do so, mice harboring chemotherapy‐naïve and chemotherapy‐resistant human ovarian cancer xenografts or patient‐derived xenografts (PDXs) were treated with the carboxyl‐terminal binding domain of the Clostridium perfringens enterotoxin (c‐CPE) conjugated to FITC (FITC‐c‐CPE) or the near‐infrared (NIR) fluorescent tag IRDye CW800 (CW800‐c‐CPE) either intraperitoneally (IP) or intravenously (IV). We found tumor fluorescence to plateau at 30 min after IP injection of both the FITC‐c‐CPE and the CW800‐c‐CPE peptides and to be significantly higher than in healthy organs (p 
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.29632