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Proceedings Paper

Tumor hypoxia fluorescence imaging using 2-nitroimidazole [i]bis[/i]-carboxylic acid indocyanine dye conjugate
Author(s): Nrusingh C. Biswal; Christopher Pavlik; Michael B. Smith; Andres Aguirre; Saeid Zanganeh; Yan Xu; Liisa T. Kuhn; Kevin P. Claffey; Quing Zhu
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Paper Abstract

We present tumor hypoxia mapping by diffuse optical fluorescence tomography. A novel 2-nitroimidazole bis-carboxylic acid indocyanine dye conjugate has been developed for tumor-targeted hypoxia fluorescence imaging. The hypoxia probe has been evaluated in-vitro using 4T1 tumor cell lines and in-vivo tumor targeting in mice. In-vivo tumor targeting in six mice demonstrated that a measured half-life of 2-nitroimidazole-indocyanine dye wash out in the tumor was significantly longer (112±32.37 minutes) than that of bis-carboxylic acid indocyanine dye (69.75±14.01 minutes). The bis-carboxylic acid indocyanine dye was completely washed out from the tumor site within 3-5 hours post-injection, but 2-nitroimidazole-ICG remained for up to 21 hours in the tumor site. Near infrared fluorescence images of mice tumors showed a 2.6-fold contrast of dye uptake with hypoxic conjugate injection (7.46±1.68 μM) compared to that with indocyanine dye injection (2.9±0.60 μM). The in-vitro cell studies were performed to assess fluorescence labeling comparing hypoxia to normoxia conditions. A fluorescence emission ratio of 2.5-fold was found between the cells treated with the 2-nitroimidazole-indocyanine dye and incubated under hypoxia compared to the cells in normoxia condition. Hypoxia specificity was also confirmed when compared to cells treated with unconjugated indocyanine dye alone. Fluorescence images acquired using a Li-COR scanner from harvested tumor samples support the in vivo monitoring and imaging results.

Paper Details

Date Published: 17 February 2011
PDF: 8 pages
Proc. SPIE 7896, Optical Tomography and Spectroscopy of Tissue IX, 78962R (17 February 2011); doi: 10.1117/12.877216
Show Author Affiliations
Nrusingh C. Biswal, Univ. of Connecticut (United States)
Christopher Pavlik, Univ. of Connecticut (United States)
Michael B. Smith, Univ. of Connecticut (United States)
Andres Aguirre, Univ. of Connecticut (United States)
Saeid Zanganeh, Univ. of Connecticut (United States)
Yan Xu, Univ. of Connecticut (United States)
Liisa T. Kuhn, Univ. of Connecticut Health Ctr. (United States)
Kevin P. Claffey, Univ. of Connecticut Health Ctr. (United States)
Quing Zhu, Univ. of Connecticut (United States)


Published in SPIE Proceedings Vol. 7896:
Optical Tomography and Spectroscopy of Tissue IX
Bruce Jason Tromberg; Arjun G. Yodh; Mamoru Tamura; Eva Marie Sevick-Muraca; Robert R. Alfano, Editor(s)

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