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A cell permeable peptide analog as a potential-specific PET imaging probe for prostate cancer detection

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Abstract

Non-invasive detection of prostate cancer or metastases still remains a challenge in the field of molecular imaging. In our recent work of screening arginine- or lysine-rich peptides for intracellular delivery of a therapeutic agent into prostate cancer cells, an arginine-rich cell permeable peptide (NH2GR11) was found with an unexpectedly preferential uptake in prostate cancer cell lines. The goal of this work was to develop this peptide as a positron emission tomography (PET) imaging probe for specific detection of distant prostate cancer metastases. The optimal length of arginine-rich peptides was evaluated by the cell uptake efficiency of three fluorescein isothiocyanate (FITC)-tagged oligoarginines (NHGR9, NHGR11, and NHGR13) in four human prostate cell lines (LNCaP, PZ-HPV-7, DU145, and PC3). Of the three oligoarginines, NH2GR11 showed the highest cell uptake and internalization efficiency with its subcellular localization in cytosol. The biodistribution of FITC-NHGR9, FITC-NHGR11, and FITC-NHGR13 performed in control nude mice displayed the unique preferential accumulation of FITC-NHGR11 in the prostate tissue. Further in vivo evaluation of FITC-NHGR11 in PC3 tumor-bearing nude mice revealed elevated uptake of this peptide in tumors as compared to other organs. In vivo pharmacokinetics evaluated with 64Cu-labeled NH2GR11 showed that the peptide was rapidly cleared from the blood (t 1/2 = 10.7 min) and its elimination half-life was 17.2 h. The PET imaging specificity of 64Cu-labled NH2GR11 was demonstrated for the detection of prostate cancer in a comparative imaging experiment using two different human cancer xenograft models.

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Acknowledgments

This work was partially supported by the Prostate Cancer Research Program of the United States Army Medical Research and Materiel Command (W81XWH-08-1-0305 and W81XWH-04-1-0222), a Clinical Innovator Award from the Flight Attendant Medical Research Institute, and a small animal imaging research program grant (SAIRP) from the National Institute of Cancer (U24 CA126608). The authors acknowledge the generous support of a private donor that allowed the purchase of the Siemens Inveon PET-CT Multi-modality System.

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Authors and Affiliations

  1. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Guiyang Hao, Yi Guo, Michael A. Long & Tiffani Anthony

  2. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Jian Zhou, Jennifer Stanfield & Jer-Tsong Hsieh

  3. Department of Radiology, Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Xiankai Sun

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  1. Guiyang Hao
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  4. Michael A. Long
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Correspondence to Jer-Tsong Hsieh or Xiankai Sun.

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Hao, G., Zhou, J., Guo, Y. et al. A cell permeable peptide analog as a potential-specific PET imaging probe for prostate cancer detection. Amino Acids 41, 1093–1101 (2011). https://doi.org/10.1007/s00726-010-0515-5

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  • DOI: https://doi.org/10.1007/s00726-010-0515-5

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