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Tumor Characterization with Dynamic Contrast Enhanced Magnetic Resonance Imaging and Biodegradable Macromolecular Contrast Agents in Mice

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Abstract

Purpose

To investigate the efficacy of polydisulfide-based biodegradable macromolecular contrast agents of different degradability and molecular weight for tumor characterization based on angiogenesis using dynamic contrast enhanced MRI (DCE-MRI).

Methods

Biodegradable macromolecular MRI contrast agents, Gd-DTPA cystamine copolymers (GDCC) and Gd-DTPA cystine copolymers (GDCP), with molecular weight of 20 and 70 KDa were evaluated for tumor characterization. Gd(DTPA-BMA) and a prototype of macromolecular contrast agent, albumin-(Gd-DTPA), were used as controls. The DCE-MRI studies were performed in nude mice bearing MDA PCa 2b and PC-3 human prostate tumor xenografts. Tumor angiogenic kinetic parameters including endothelium transfer coefficient (Ktrans) and fractional tumor plasma volume (fPV) were calculated from the DCE-MRI data using a two-compartment model and compared between the two different tumor models for each contrast agent.

Results

There was no significant difference in the fPV values between two tumor models estimated with the same agent except for GDCC-70. The Ktrans values in both tumor models decreased with the increase of molecular weight of contrast agents. With the same high molecular weight (70 KDa), GDCC-70 showed a higher Ktrans values than GDCP-70 due to high degradability of the former in both tumor models (p < 0.05). The Ktrans values of MDA PCa 2b tumors were significantly higher than those of PC-3 tumors estimated by Gd(DTPA-BMA), GDCC-20, GDCC-70, GDCP-70, and albumin-(Gd-DTPA) (p < 0.05).

Conclusions

The polydisulfide-based biodegradable macromolecular MRI contrast agents are promising in tumor characterization and differentiation with dynamic contrast enhanced MRI.

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Acknowledgements

The authors thank Dr. Yong-En Sun for his technique in the tail vein catheterization and Melody Johnson for the operation of MRI scanner. This work is supported in part by the NIH grant R01 EB000489.

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA

    Xueming Wu & Zheng-Rong Lu

  2. Department of Materials Science and Engineering, University of Utah, Salt Lake City, Utah, USA

    Yi Feng

  3. Department of Radiology, University of Utah, Salt Lake City, Utah, USA

    Eun-Kee Jeong

  4. Department of Pathology, University of Utah, Salt Lake City, Utah, USA

    Lyska Emerson

  5. Department of Biomedical Engineering, Case Western Reserve University, Wickenden 427, 10900 Euclid Avenue, Cleveland, Ohio, 44106-7207, USA

    Zheng-Rong Lu

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  1. Xueming Wu
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  2. Yi Feng
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  5. Zheng-Rong Lu
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Correspondence to Zheng-Rong Lu.

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Xueming Wu and Yi Feng made equal contribution in this work.

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Wu, X., Feng, Y., Jeong, EK. et al. Tumor Characterization with Dynamic Contrast Enhanced Magnetic Resonance Imaging and Biodegradable Macromolecular Contrast Agents in Mice. Pharm Res 26, 2202–2208 (2009). https://doi.org/10.1007/s11095-009-9935-x

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  • DOI: https://doi.org/10.1007/s11095-009-9935-x

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