Near-infrared fluorescence imaging of gastrin releasing peptide receptor targeting in prostate cancer lymph node metastases

Authors

  • Quan-Yu Cai,

    1. Department of Radiology, University of Missouri, Columbia, Missouri
    2. International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, Missouri
    3. Harry S. Truman Veterans' Memorial Hospital, Columbia, Missouri
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  • Ping Yu,

    1. Department of Physics and Astronomy, University of Missouri, Columbia, Missouri
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  • Cynthia Besch-Williford,

    1. IDEXX RADIL, Columbia, Missouri
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  • Charles J. Smith,

    1. Department of Radiology, University of Missouri, Columbia, Missouri
    2. Harry S. Truman Veterans' Memorial Hospital, Columbia, Missouri
    3. University of Missouri Research Reactor Center, University of Missouri, Columbia, Missouri
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  • Gary L. Sieckman,

    1. Harry S. Truman Veterans' Memorial Hospital, Columbia, Missouri
    2. Department of Internal Medicine, University of Missouri, Columbia, Missouri
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  • Timothy J. Hoffman,

    1. Harry S. Truman Veterans' Memorial Hospital, Columbia, Missouri
    2. Department of Internal Medicine, University of Missouri, Columbia, Missouri
    3. Nuclear Science & Engineering Institute, University of Missouri, Columbia, Missouri
    4. Department of Chemistry, University of Missouri, Columbia, Missouri
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  • Lixin Ma

    Corresponding author
    1. Department of Radiology, University of Missouri, Columbia, Missouri
    2. International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, Missouri
    3. Harry S. Truman Veterans' Memorial Hospital, Columbia, Missouri
    4. Nuclear Science & Engineering Institute, University of Missouri, Columbia, Missouri
    • Department of Radiology, University of Missouri, One Hospital Drive, DC069.10, Columbia, MO 65212.
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Abstract

BACKGROUND

Development of high affinity and specificity molecular imaging probes that increase accuracy for early detection of lymph node (LN) metastases is important for improving survivorship in prostate cancer. We evaluated the specificity, sensitivity, and accuracy of fluorescence-labeled bombesin (BBN) peptides to detect LN and systematic metastases in orthotopic mouse models bearing gastrin releasing peptide receptor (GRPR)-positive human prostate cancer.

METHODS

PC-3 cells were orthotopically implanted in severe combined immunedeficient or thymic nude (nu/nu) male mice. Tumor growth was monitored using magnetic resonance imaging. Alexa Fluor 680 conjugated BBN[7-14]NH2 (AF680-BBN) peptides were administered intravenously at 4–7 weeks post-tumor-implantation. Near-infrared fluorescence (NIRF) imaging was performed for up to 6 hr post-injection. The imaging sensitivity and specificity were assessed by co-registration of AF680-BBN NIRF imaging and luciferase bioluminescence imaging of the PC-3/Luc+ orthotopic mouse model.

RESULTS

AF680-BBN showed a high binding affinity and selectivity to GRPR-positive cancer in vitro and in vivo. LN and peritoneal metastases were detected by NIRF imaging, and confirmed by histopathology. Tumor-to-muscle (T/M) ratio was the highest at 2-hr post-injection (4.12 ± 1.77). Blocking experiments, using unlabeled BBN as the inhibiting agent, significantly reduced the T/M ratio (1.64 ± 0.21, P = 0.02). AF680-BBN NIRF imaging had a sensitivity of 89.4%, specificity of 92.9%, and accuracy of 90.2% for the detection of metastases in mice.

CONCULSIONS

The studies suggest the potential of use and development of NIR-fluorescent BBN probes as site-directed agents to help improve the current detection and LN staging accuracy in prostate cancer. Prostate 73: 842–854, 2013. © 2012 Wiley Periodicals, Inc.

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