Fluorescence-lifetime molecular imaging can detect invisible peritoneal ovarian tumors in bloody ascites.

Abstract

Blood contamination, such as bloody ascites or hemorrhages during surgery, is a potential hazard for clinical application of fluorescence imaging. In order to overcome this problem, we investigate if fluorescence-lifetime imaging helps to overcome this problem. Samples were prepared at concentrations ranging 0.3-2.4 μm and mixed with 0-10% of blood. Fluorescence intensities and lifetimes of samples were measured using a time-domain fluorescence imager. Ovarian cancer SHIN3 cells overexpressing the D-galactose receptor were injected into the peritoneal cavity 2.5 weeks before the experiments. Galactosyl serum albumin-rhodamine green (GSA-RhodG), which bound to the D-galactose receptor and was internalized thereafter, was administered intraperitoneally to peritoneal ovarian cancer-bearing mice with various degrees of bloody ascites. In vitro study showed a linear correlation between fluorescence intensity and probe concentration (r(2) > 0.99), whereas the fluorescence lifetime was consistent (range, 3.33 ± 0.15-3.75 ± 0.04 ns). By adding 10% of blood to samples, fluorescence intensities decreased to <1%, while fluorescence lifetimes were consistent. In vivo fluorescence lifetime of GSA-RhodG stained tumors was longer than the autofluorescence lifetime (threshold, 2.87 ns). Tumor lesions under hemorrhagic peritonitis were not depicted using fluorescence intensity imaging; however, fluorescence-lifetime imaging clearly detected tumor lesions by prolonged lifetimes. In conclusion, fluorescence-lifetime imaging with GSA-RhodG depicted ovarian cancer lesions, which were invisible in intensity images, in hemorrhagic ascites.

• Authors: Takahito Nakajima, Kohei Sano, Kazuhide Sato, Rira Watanabe, Toshiko Harada, Hirofumi Hanaoka, Peter L Choyke, Hisataka Kobayashi
• Journal: Cancer science (Cancer Sci) Vol. 105 Issue 3 Pg. 308-14 (Mar 2014) ISSN: 1349-7006 [Electronic] England
• PMID: 24479901 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published 2013. This article is a U.S. Government work and is in the public domain in the USA. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• Albumins
• Fluorescent Dyes
• Rhodamines
• galactosyl serum albumin-rhodamine green

Topics

• Albumins
• Animals
• Ascites (pathology)
• Blood Loss, Surgical
• Cell Line, Tumor
• Female
• Fluorescent Dyes
• Humans
• Mice
• Mice, Nude
• Molecular Imaging
• Neoplasm Transplantation
• Optical Imaging
• Ovarian Neoplasms (pathology)
• Peritoneal Neoplasms (secondary)
• Peritoneum (surgery)
• Rhodamines
• Whole Body Imaging