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J Biomed Opt. 2014 Jan;19(1):16022. doi: 10.1117/1.JBO.19.1.016022.

Noninvasive measurement of pharmacokinetics by near-infrared fluorescence imaging in the eye of mice.

Author information

1
Pharma Research and Early Development (pRED), Discovery Oncology, Roche Diagnostics GmbH, Nonnenwald 2, D-82377 Penzberg, Germany.
2
Large Molecule Research (LMR), Roche Diagnostics GmbH, Nonnenwald 2, D-82377 Penzberg, Germany.

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.

PMID:
24474508
DOI:
10.1117/1.JBO.19.1.016022
[Indexed for MEDLINE]
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