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Dynamic Contrast-Enhanced Folate-Receptor-Targeted MR Imaging Using a Gd-loaded PEG-Dendrimer–Folate Conjugate in a Mouse Xenograft Tumor Model

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Abstract

Purpose

The purpose of this study is to validate a folate-receptor (FR)-targeted dendrimer, PEG-G3-(Gd-DTPA)11-(folate)5, for its ability to detect FR-positive tumors, by using dynamic contrast-enhanced MRI.

Procedures

KB cells, FR siRNA knockdown KB cells, and FR negative HT-1080 cells, were incubated with fluorescein-labeled dendrimer and their cellular uptake was observed. Dynamic contrast-enhanced MRI was performed on mice-bearing KB and HT-1080 tumors and the enhancement patterns and parameters were analyzed.

Results

Green fluorescence was found in the KB cells in the cellular uptake experiment, but was not seen in other settings. In the dynamic contrast-enhanced MRI, the 30-min washout percentage was −4 ± 18% in the KB tumors and 39 ± 23% in the HT-1080 tumors. A 17% cut-off point gave a sensitivity of 94.4% and a specificity of 93.8%.

Conclusions

We have demonstrated the targeting ability of PEG-G3-(Gd-DTPA)11-(folate)5 in vitro and in vivo. A 17% cut-off point for a 30-min washout percentage can be a useful parameter for the diagnosis of FR-positive tumors.

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Acknowledgments

This research was supported in part by National Science Council grants 95-2314-B-532-005 and 96-2321-B-532-0001. We thank Mr. Hsiau Yu Yo and Mr. Wei Ju Hsu for their diligent laboratory work.

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Authors and Affiliations

  1. Department of Radiology, Taipei City Hospital, Taipei, Taiwan

    Wei-Tsung Chen, Ran-Chou Chen & Shin-Yang Tu

  2. Department of Radiology, School of Medicine, National Taiwan University, Taipei, Taiwan

    Wei-Tsung Chen & Tiffany Ting-Fang Shih

  3. Union Chemical Laboratory, Industrial Technology Research Institute, Hsinchu, Taiwan

    Dhakshanamurthy Thirumalai & Chin-I Lin

  4. Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

    Tiffany Ting-Fang Shih

  5. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan

    Ran-Chou Chen

  6. Department of Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Pang-Chyr Yang

  7. Department of Medicine, School of Medicine, National Taiwan University, Taipei, Taiwan

    Pang-Chyr Yang

Authors
  1. Wei-Tsung Chen
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  2. Dhakshanamurthy Thirumalai
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  3. Tiffany Ting-Fang Shih
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  4. Ran-Chou Chen
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  5. Shin-Yang Tu
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  6. Chin-I Lin
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Corresponding author

Correspondence to Tiffany Ting-Fang Shih.

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Supplementary figure 1

Immunoperoxidase KB cell staining for the folate receptor. Positive immunoreactions appeared as dark brown staining on the KB cell surfaces. Magnification, ×400. (JPG 101 KB)

Supplementary figure 2

The 1H NMR spectrum of the PEG-bis[G-3]-(OH)8. The spikes of G1and G2 methyl protons merged together at δ 1.61. However, the intensity ratio of the merged spike and the singlet of G3 methyl protons was 3:4 [(a + b):c = (1 + 2):4]. (GIF 182 KB)

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Chen, WT., Thirumalai, D., Shih, T.TF. et al. Dynamic Contrast-Enhanced Folate-Receptor-Targeted MR Imaging Using a Gd-loaded PEG-Dendrimer–Folate Conjugate in a Mouse Xenograft Tumor Model. Mol Imaging Biol 12, 145–154 (2010). https://doi.org/10.1007/s11307-009-0248-6

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  • DOI: https://doi.org/10.1007/s11307-009-0248-6

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