Fluorescence-lifetime molecular imaging can detect invisible peritoneal ovarian tumors in bloody ascites.
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.
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MA, USA.
Takahito
T
Nakajima
Kohei
K
Sano
Kazuhide
K
Sato
Rira
R
Watanabe
Toshiko
T
Harada
Hirofumi
H
Hanaoka
Peter L
PL
Choyke
Hisataka
H
Kobayashi
D000418:Albumins; D000818:Animals; D001201:Ascites / Q000473:pathology*; D016063:Blood Loss, Surgical; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D010051:Ovarian Neoplasms / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000556:secondary*; D010537:Peritoneum / Q000601:surgery; D012235:Rhodamines; D051598:Whole Body Imaging
D000418:Albumins; D005456:Fluorescent Dyes; D012235:Rhodamines; C588184:galactosyl serum albumin-rhodamine green
Fluorescence lifetime; fluorescence-guided surgery; hemorrhagic ascites; molecular imaging; ovarian cancer