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Multi-targeted multi-color in vivo optical imaging in a model of disseminated peritoneal ovarian cancer.

Abstract
Commonly used in flow cytometry, multiplexed optical probes can diagnose multiple types of cell surface marker, potentially leading to improved diagnosis accuracy in vivo. Herein, we demonstrate the targeting of two different tumor markers in models of disseminated ovarian cancer. Two ovarian cancer cell lines (SKOV3 and SHIN3) were employed; both overexpress D-galactose receptor (D-galR), but only SKOV3 overexpresses HER2/neu. Additionally, fusion tumors composed of SKOV3 and SHIN3/RFP were evaluated. Both galactosyl serum albumin-rhodamine green (GSA-RhodG), which binds D-galR, and trastuzumab-Alexa680, which binds HER2/neu, were administered to tumor-bearing mice for in vivo fluorescence imaging and in situ fluorescence microscopy. In vivo fluorescence imaging depicted 64 of 69 SKOV3 tumors (94.2%) based on their dual spectra corresponding to both RhodG and Alexa680, while all 71 SHIN3 tumors (100%) were detected based on their single spectrum corresponding only to RhodG. All 59 SHIN3 and 36 SKOV3 tumors were correctly diagnosed with in situ microscopy. Additionally, in the mixed tumor model, all tumors could be depicted using the RhodG spectrum, but only SKOV3 components also showed the Alexa680 spectrum. In conclusion, multitargeted multicolor optical imaging enabled specific in vivo diagnosis of tumors expressing distinct patterns of receptors, leading to improved diagnostic accuracy.
AuthorsNobuyuki Kosaka, Mikako Ogawa, Michelle R Longmire, Peter L Choyke, Hisataka Kobayashi
JournalJournal of biomedical optics (J Biomed Opt) 2009 Jan-Feb Vol. 14 Issue 1 Pg. 014023 ISSN: 1083-3668 [Print] United States
PMID19256711 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Albumins
  • Rhodamines
  • galactosyl serum albumin-rhodamine green
Topics
  • Albumins
  • Animals
  • Cell Line, Tumor
  • Colorimetry (methods)
  • Disease Models, Animal
  • Female
  • Humans
  • Image Enhancement (methods)
  • Mice
  • Microscopy, Fluorescence, Multiphoton (methods)
  • Ovarian Neoplasms (pathology)
  • Peritoneal Neoplasms (pathology)
  • Reproducibility of Results
  • Rhodamines
  • Sensitivity and Specificity

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