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In Vivo Pharmacokinetics Assessment of Indocyanine Green-Loaded Nanoparticles in Tumor Tissue with a Dynamic Diffuse Fluorescence Tomography System

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Abstract

Purpose

The purpose of this study was to show a systematic strategy for assessing the pharmacokinetics of indocyanine green (ICG)-loaded nanoparticles in the tumor tissue based on a dynamic diffuse fluorescence tomography (DFT) system.

Procedures

Twelve-seven-week-old male Balb/c nude mice bearing HepG2/ADR hepatocellular carcinoma were randomly divided into four groups (n = 3 per group). Four hundred microliters of three types of ICG-loaded nanoparticles (content of ICG: 50 μg/ml) and free ICG (50 μg/ml) was intravenously injected into the mice in each group, respectively. Afterwards, the real-time tomographic images on the spatial level were acquired at 2–11 min, 30 min, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h post-injection, and pharmacokinetic rates were derived for semi-quantitative assessment of the pharmacokinetics of nanoparticles at the tumor site using our proposed pharmacokinetic analysis method.

Results

The results obtained from our proposed dynamic DFT experiment demonstrated the distribution of different ICG formulations on the spatial level and enabled the semi-quantitative analysis of the pharmacokinetics of nanoparticles in the tumor tissue.

Conclusions

The obtained pharmacokinetic rates effectively reflected the metabolic processes of nanoparticles in the tumor tissue, which proves to be beneficial for the development of tumor diagnosis and therapy.

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Acknowledgments

The authors would like to acknowledge funding support from the National Natural Science Foundation of China and Tianjin Municipal Government of China.

Funding

This study was funded by the National Natural Science Foundation of China (61475115, 81671728, 61475116, 61575140, 81571723, 81771880) and Tianjin Municipal Government of China (17JCZDJC32700, 18JCYBJC29400).

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Correspondence to Limin Zhang or Feng Gao.

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All applicable institutional and/or national guidelines for the care and use of animals were followed.

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Zhang, Y., Zhang, L., Yin, G. et al. In Vivo Pharmacokinetics Assessment of Indocyanine Green-Loaded Nanoparticles in Tumor Tissue with a Dynamic Diffuse Fluorescence Tomography System. Mol Imaging Biol 21, 1044–1053 (2019). https://doi.org/10.1007/s11307-019-01340-7

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