Amino Acids

, Volume 41, Issue 5, pp 1093–1101

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

  • Guiyang Hao
  • Jian Zhou
  • Yi Guo
  • Michael A. Long
  • Tiffani Anthony
  • Jennifer Stanfield
  • Jer-Tsong Hsieh
  • Xiankai Sun
Original Article

DOI: 10.1007/s00726-010-0515-5

Cite this article as:
Hao, G., Zhou, J., Guo, Y. et al. Amino Acids (2011) 41: 1093. doi:10.1007/s00726-010-0515-5

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 (t1/2 = 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.

Keywords

PET Prostate cancer Cell permeable peptide 64Cu 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Guiyang Hao
    • 1
  • Jian Zhou
    • 2
  • Yi Guo
    • 1
  • Michael A. Long
    • 1
  • Tiffani Anthony
    • 1
  • Jennifer Stanfield
    • 2
  • Jer-Tsong Hsieh
    • 2
  • Xiankai Sun
    • 3
  1. 1.Department of RadiologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of UrologyUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Department of Radiology, Advanced Imaging Research CenterUniversity of Texas Southwestern Medical CenterDallasUSA

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