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Journal of Biomedical Optics • Open Access

High-sensitivity detection of breast tumors in vivo by use of a pH-sensitive near-infrared fluorescence probe
Author(s): Julia E. Mathejczyk; Frauke Alves; Joanna Napp; Jutta Pauli; Ute Resch-Genger; Christian Dullin

Paper Abstract

We investigated the potential of the pH-sensitive dye, CypHer5E, conjugated to Herceptin (pH-Her) for the sensitive detection of breast tumors in mice using noninvasive time-domain near-infrared fluorescence imaging and different methods of data analysis. First, the fluorescence properties of pH-Her were analyzed as function of pH and/or dye-to-protein ratio, and binding specificity was confirmed in cell-based assays. Subsequently, the performance of pH-Her in nude mice bearing orthotopic HER2-positive (KPL-4) and HER2-negative (MDA-MB-231) breast carcinoma xenografts was compared to that of an always-on fluorescent conjugate Alexa Fluor 647-Herceptin (Alexa-Her). Subtraction of autofluorescence and lifetime (LT)-gated image analyses were performed for background fluorescence suppression. In mice bearing HER2-positive tumors, autofluorescence subtraction together with the selective fluorescence enhancement of pH-Her solely in the tumor's acidic environment provided high contrast-to-noise ratios (CNRs). This led to an improved sensitivity of tumor detection compared to Alexa-Her. In contrast, LT-gated imaging using LTs determined in model systems did not improve tumor-detection sensitivity in vivo for either probe. In conclusion, pH-Her is suitable for sensitive in vivo monitoring of HER2-expressing breast tumors with imaging in the intensity domain and represents a promising tool for detection of weak fluorescent signals deriving from small tumors or metastases.

Paper Details

Date Published: 27 July 2012
PDF: 10 pages
J. Biomed. Opt. 17(7) 076028 doi: 10.1117/1.JBO.17.7.076028
Published in: Journal of Biomedical Optics Volume 17, Issue 7
Show Author Affiliations
Julia E. Mathejczyk, Max-Planck-Institut für experimentelle Medizin (Germany)
Frauke Alves, Max-Planck-Institut für experimentelle Medizin (Germany)
Joanna Napp, Max-Planck-Institut für experimentelle Medizin (Germany)
Jutta Pauli, Bundesanstalt für Materialforschung und -prüfung (Germany)
Ute Resch-Genger, Bundesanstalt für Materialforschung und -prüfung (Germany)
Christian Dullin, Univ. Medicine Göttingen (Germany)

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