Characteristics of ovarian cancer detection by a near-infrared fluorescent probe activated by human NAD(P)H: quinone oxidoreductase isozyme 1 (hNQO1)
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Yuko Nakamura1, Zhenhua Shen2, Toshiko Harada1, Tadanobu Nagaya1, Kazuhide Sato1, Shuhei Okuyama1, Fusa Ogata1, Peter L. Choyke1, Robin L. McCarley2 and Hisataka Kobayashi1
1Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, United States National Institutes of Health, Bethesda, Maryland 20892-1088, USA
2Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803-1804, USA
Hisataka Kobayashi, email: [email protected]
Keywords: near-infrared emitting probe, human NAD(P)H: quinone oxidoreductase isozyme 1, green light-emitting probe, kinetic map, peritoneal cancer metastases
Received: March 10, 2017 Accepted: April 12, 2017 Published: May 20, 2017
Near-infrared (NIR) fluorescent probes are ideal for in vivo imaging, because they offer deeper tissue penetration by the light and lower background autofluorescence than fluorophores that emit in the visible range. Q3STCy is a newly synthesized, NIR light-emitting probe that is activated by an enzyme commonly overexpressed in tumor cells, human nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase isozyme 1, known as hNQO1 or DT-diaphorase. The purpose of this study is to compare the sensitivity of detecting peritoneal ovarian cancer metastasis (POCM) with Q3STCy and gGlu-HMRG, a green fluorescent probe, upon their surface application. In vitro uptake of Q3STCy was significantly higher than that of gGlu-HMRG. Using a red fluorescence protein (RFP)-labeled in vivo tumor model of POCM, the Q3STCy probe provided high sensitivity (96.9%) but modest specificity (61.0%), most likely the result of albumin-probe interactions and non-specific activation in nearby altered but healthy cells. Three types of kinetic maps based on maximum fluorescence signal (MF), wash-in rate (WIR), and area under the curve (AUC) allowed for differentiation of the activated fluorescence signal associated with POCM from the background signal of the small intestine, thereby significantly improving the specificity of Q3STCy to 80%, 100%, and 100% for MF, WIR, and AUC, as well yielding a moderate improvement in sensitivity (100% for all approaches) that is comparable to that with gGlu-HMRG, but with the added advantages of NIR fluorescence as the transduction modality. Such a new methodology has the potential to afford identification of cancerous lesions deeper within tissue.
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