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Journal of Biomedical Optics • Open Access

Noninvasive measurement of pharmacokinetics by near-infrared fluorescence imaging in the eye of mice
Author(s): Michael Dobosz; Steffen Strobel; Kay-Gunnar Stubenrauch; Franz Osl; Werner Scheuer

Paper Abstract

Purpose: For generating preclinical pharmacokinetics (PKs) of compounds, blood is drawn at different time points and levels are quantified by different analytical methods. In order to receive statistically meaningful data, 3 to 5 animals are used for each time point to get serum peak-level and half-life of the compound. Both characteristics are determined by data interpolation, which may influence the accuracy of these values. We provide a method that allows continuous monitoring of blood levels noninvasively by measuring the fluorescence intensity of labeled compounds in the eye and other body regions of anesthetized mice. Procedures: The method evaluation was performed with four different fluorescent compounds: (i) indocyanine green, a nontargeting dye; (ii) OsteoSense750, a bone targeting agent; (iii) tumor targeting Trastuzumab-Alexa750; and (iv) its F(ab ′ ) 2 -alxea750 fragment. The latter was used for a direct comparison between fluorescence imaging and classical blood analysis using enzyme-linked immunosorbent assay (ELISA). Results: We found an excellent correlation between blood levels measured by noninvasive eye imaging with the results generated by classical methods. A strong correlation between eye imaging and ELISA was demonstrated for the F(ab ′ ) 2 fragment. Whole body imaging revealed a compound accumulation in the expected regions (e.g., liver, bone). Conclusions: The combination of eye and whole body fluorescence imaging enables the simultaneous measurement of blood PKs and biodistribution of fluorescent-labeled compounds.

Paper Details

Date Published: 27 January 2014
PDF: 9 pages
J. Biomed. Opt. 19(1) 016022 doi: 10.1117/1.JBO.19.1.016022
Published in: Journal of Biomedical Optics Volume 19, Issue 1
Show Author Affiliations
Michael Dobosz, Roche Diagnostics GmbH (Germany)
Steffen Strobel, Roche Diagnostics GmbH (Germany)
Kay-Gunnar Stubenrauch, Roche Diagnostics GmbH (Germany)
Franz Osl, Roche Diagnostics GmbH (Germany)
Werner Scheuer, Roche Diagnostics GmbH (Germany)

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