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    Characterization of TCP-1 probes for molecular imaging of colon cancer.

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    JCR Final Accepted Manuscript_ ...
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    Author
    Liu, Zhonglin
    Gray, Brian D
    Barber, Christy
    Bernas, Michael
    Cai, Minying
    Furenlid, Lars R
    Rouse, Andrew
    Patel, Charmi
    Banerjee, Bhaskar
    Liang, Rongguang
    Gmitro, Arthur F
    Witte, Marlys H
    Pak, Koon Y
    Woolfenden, James M
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    Issue Date
    2016-10-10
    Keywords
    Colorectal cancer
    Molecular Imaging
    Tc-99m
    SPECT
    Mouse xenograft models
    Peptide
    
    Metadata
    Show full item record
    Citation
    Characterization of TCP-1 probes for molecular imaging of colon cancer. 2016, 239:223-30 J Control Release
    Journal
    Journal of controlled release : official journal of the Controlled Release Society
    Rights
    © 2016 Elsevier B.V. All rights reserved.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Molecular probes capable of detecting colorectal cancer (CRC) are needed for early CRC diagnosis. The objective of this study was to characterize c[CTPSPFSHC]OH (TCP-1), a small peptide derived from phage display selection, for targeting human CRC xenografts using technetium-99m ((99m)Tc)-labeled TCP-1 and fluorescent cyanine-7 (Cy7)-labeled form of the peptide (Cy7-TCP-1). (99m)Tc-TCP-1 was generated by modifying TCP-1 with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC) followed by radiolabeling. In vitro saturation binding experiments were performed for (99m)Tc-TCP-1 in human HCT116 colon cancer cells. SCID mice with human HCT116 cancer xenografts were imaged with (99m)Tc-TCP-1 or control peptide using a small-animal SPECT imager: Group I (n=5) received no blockade; Group II (n=5) received a blocking dose of non-radiolabeled TCP-1. Group III (n=5) were imaged with (99m)Tc-labeled control peptide (inactive peptide). SCID mice with human PC3 prostate cancer xenografts (Group IV, n=5) were also imaged with (99m)Tc-TCP-1. Eight additional SCID mice bearing HCT116 xenografts in dorsal skinfold window chambers (DSWC) were imaged by direct positron imaging of (18)F-fluorodeoxyglucose ((18)F-FDG) and fluorescence microscopy of Cy7-TCP-1. In vitro(99m)Tc-HYNIC-TCP-1 binding assays on HCT 116 cells indicated a mean Kd of 3.04±0.52nM. In cancer xenografts, (99m)Tc-TCP-1 radioactivity (%ID/g) was 1.01±0.15 in the absence of blockade and was reduced to 0.26±0.04 (P<0.01) with blockade. No radioactive uptake was observed in the PC3 tumors with (99m)Tc-TCP-1 or HCT116 tumors with inactive peptide. Cy7-TCP-1 activity localized not only in metabolically active tumors, as defined by (18)F-FDG imaging, but also in peritumoral microvasculature. In conclusion, TCP-1 probes may have a distinct targeting mechanism with high selectivity for CRC and tumor-associated vasculature. Molecular imaging with TCP-1 probes appears promising to detect malignant colorectal lesions.
    ISSN
    1873-4995
    PubMed ID
    27574992
    DOI
    10.1016/j.jconrel.2016.08.033
    Version
    Final accepted manuscript
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jconrel.2016.08.033
    Scopus Count
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