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Evaluation of Tc-99 m Labeled Dimeric GX1 Peptides for Imaging of Colorectal Cancer Vasculature

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Abstract

Purpose

This study aimed to evaluate the potential of PEGylated dimeric GX1 peptide as a radiotracer for imaging of colorectal cancer vasculature in a LoVo tumor xenografted mouse model.

Procedures

The [99mTc]PEG-(GX1)2 peptide was synthesized and identified. Confocal immunofluorescence analysis, receptor binding assay, and competitive inhibition assay were performed to evaluate the binding specificity and the receptor binding affinity of PEG-(GX1)2 to Co-human umbilical vein endothelial cells (HUVECs). Single photon emission computed tomography imaging and biodistribution were performed to evaluate the targeting ability of PEG-(GX1)2 to colorectal cancer.

Results

The studies in vitro suggested that PEG-(GX1)2 co-localized with Factor VIII in the perinuclear cytoplasm of Co-HUVECs and bound specifically to Co-HUVECs with a high affinity. The studies in vivo demonstrated that the targeting efficacy of PEG-(GX1)2 was superior to GX1.

Conclusions

PEGylation improved the affinity and the targeting ability of the GX1 peptide. PEG-(GX1)2 is a more promising probe for imaging of colorectal vasculature than GX1.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81090270, No. 81090273, No. 81471717 and No. 81371615), the National Key and Basic Research Development Program of China (No. 2010CB529302), and Natural Science Foundation of Shaanxi Province (2013 K12-05-11). We thank Dr. Zhe Wang and Wenhui Ma for their help in SPECT imaging.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Author notes

    Authors and Affiliations

    1. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

      Jipeng Yin, Liping Yao, Ming Li, Hao Hu, Jing Zhang, Yongzhan Nie & Kaichun Wu

    2. First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China

      Xiaoli Hui

    3. The 88th Hospital of PLA, Taian, China

      Bo Xin

    4. School of Life Science, Dalian Nationalities University, Dalian, China

      Minglei He

    5. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China

      Jing Wang

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    1. Jipeng Yin
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    Correspondence to Kaichun Wu.

    Additional information

    Jipeng Yin, Xiaoli Hui and Liping Yao contributed equally to this work.

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    Yin, J., Hui, X., Yao, L. et al. Evaluation of Tc-99 m Labeled Dimeric GX1 Peptides for Imaging of Colorectal Cancer Vasculature. Mol Imaging Biol 17, 661–670 (2015). https://doi.org/10.1007/s11307-015-0838-4

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