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

• Published in: Cancer science Vol. 105; no. 3; pp. 308 - 314
• Main Authors: Nakajima, Takahito, Sano, Kohei, Sato, Kazuhide, Watanabe, Rira, Harada, Toshiko, Hanaoka, Hirofumi, Choyke, Peter L., Kobayashi, Hisataka
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.03.2014; BlackWell Publishing Ltd
• Subjects: Albumins; Animals; Ascites; Ascites - pathology; Blood; Blood Loss, Surgical; Cameras; Cell Line, Tumor; Contamination; Female; Fluids; Fluorescence; Fluorescence lifetime; fluorescence‐guided surgery; Fluorescent Dyes; Galactose; Hemorrhage; hemorrhagic ascites; Humans; Laboratory animals; Lifetime; Medical research; Metastasis; Mice; Mice, Nude; Molecular Imaging; Neoplasm Transplantation; Optical Imaging; Original; Ovarian cancer; Ovarian Neoplasms - pathology; Peritoneal Neoplasms - secondary; Peritoneum; Peritoneum - surgery; Peritonitis; Proteins; Rhodamine; Rhodamines; Surgeons; Surgery; Tumors; Whole Body Imaging; United States > US; fluorescence-guided surgery; hemorrhagic ascites; Fluorescence lifetime; molecular imaging; ovarian cancer
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12343

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 (r2 > 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. Fluorescence life time imaging (FLTI) is a new optical imaging technology for depicting cancer using molecular targeting imaging probe. FLTI can detect cancer by fluorescence lifetime even without sufficient contrast on photon intensity in fluorescence images, therefore, FLTI can be another new eye of surgeons or endoscopy physicians for finding cancer even under high auto‐fluorescence background or in the bloody fluid/ascites.