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The Labeling, Visualization, and Quantification of Hyaluronan Distribution in Tumor-Bearing Mouse Using PET and MR Imaging

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Abstract

Purpose

Hyaluronan (HA) based biomaterials are widely used as tissue scaffolds, drug formulations, as well as targeting ligands and imaging probes for diagnosis and drug delivery. However, because of the presence of abundant endogenous HA presented in various tissues in vivo, the pharmacokinetic behavior and biodistribution patterns of exogenously administered HAs have not been well characterized.

Methods

The HA backbone was modified with Diethylenetriamine (DTPA) to enable the chelation of gadolinium (Gd) and aluminum (Al) ions. Series of PET and MR imaging were taken after the injection of HA-DTPA-Gd and HA-DTPA-Al18F while using18F-FDG and Magnevist(DTPA-Gd) as controls. The Tomographic images were analyzed and quantified to reveal the distribution and locations of HA in tumor-bearing mice.

Results

The labeled HAs had good stability in plasma. They retained binding affinity towards CD44s on tumor cell surface. The injected HAs distributed widely in various organs, but were found to be cleared quickly except inside tumor tissues where the signals were higher and persisted longer.

Conclusion

Medical imaging tools, including MR and PET, can be highly valuable for examining biomaterial distribution non-invasively. The HA tumor accumulation properties may be explored for the development of active targeting drug carriers and molecular probes.

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Abbreviations

CCK-8:

Cell counting Kit-8

DTPA:

Diethylenetriamine pentoacetic acid

FBS:

Fetal bovine serum

FOV:

Fields of view

HA:

Hyaluronan

HEC:

Hepato-enteric circulation

PET/CT:

Positron emission tomography/computed tomography

PET/MR:

Positron emission tomography/magnetic resonance

MRI:

Magnetic resonance imaging

NMR:

Nuclear magnetic resonance

RES:

Reticuloendothelial System

ROI:

Regions of interest

SNR:

Signal-to-noise ratio

SPECT:

Single-photon emission computed tomography

SUV:

Standardized uptake value

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ACKNOWLEDGMENTS AND DISCLOSURES

We would like to thank Shanghai Atom Kexing Pharmaceuticals Co., Ltd., for supplying the 18F fluorine. This study was supported by the National Natural Science Foundation of China (No. 81571787 and 81690262), Ruijin Youth NSFC Cultivation Fund (No. 2019QNPY02019), and the Medical-Engineering Joint Fund of Shanghai Jiao Tong University (No. YG2015MS54).

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Authors and Affiliations

  1. School of Pharmacy, Shanghai Jiao Tong University, No.800, Dongchuan Rd., Shanghai, 200240, People’s Republic of China

    Wangxi Hai, Xiao Bao, Kang Sun & Jinliang Peng

  2. Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Biao Li

  3. School of Pharmacy and Chemistry, Dali University, Xia Guan, Dali, Yunnan, 6710000, People’s Republic of China

    Yuhong Xu

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  1. Wangxi Hai
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Correspondence to Jinliang Peng or Yuhong Xu.

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Hai, W., Bao, X., Sun, K. et al. The Labeling, Visualization, and Quantification of Hyaluronan Distribution in Tumor-Bearing Mouse Using PET and MR Imaging. Pharm Res 37, 237 (2020). https://doi.org/10.1007/s11095-020-02957-y

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