Phage display peptide probes for imaging early response to bevacizumab treatment |
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Authors: | Qizhen Cao Shuanglong Liu Gang Niu Kai Chen Yongjun Yan Zhaofei Liu Xiaoyuan Chen |
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Institution: | (1) Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA;(2) Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD 20892-2281, USA; |
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Abstract: | Early evaluation of cancer response to a therapeutic regimen can help increase the effectiveness of treatment schemes and,
by enabling early termination of ineffective treatments, minimize toxicity, and reduce expenses. Biomarkers that provide early
indication of tumor therapy response are urgently needed. Solid tumors require blood vessels for growth, and new anti-angiogenic
agents can act by preventing the development of a suitable blood supply to sustain tumor growth. The purpose of this study
is to develop a class of novel molecular imaging probes that will predict tumor early response to an anti-angiogenic regimen
with the humanized vascular endothelial growth factor antibody bevacizumab. Using a bevacizumab-sensitive LS174T colorectal
cancer model and a 12-mer bacteriophage (phage) display peptide library, a bevacizumab-responsive peptide (BRP) was identified
after six rounds of biopanning and tested in vitro and in vivo. This 12-mer peptide was metabolically stable and had low toxicity
to both endothelial cells and tumor cells. Near-infrared dye IRDye800-labeled BRP phage showed strong binding to bevacizumab-treated
tumors, but not to untreated control LS174T tumors. In addition, both IRDye800- and 18F-labeled BRP peptide had significantly higher uptake in tumors treated with bevacizumab than in controls treated with phosphate-buffered
saline. Ex vivo histopathology confirmed the specificity of the BRP peptide to bevacizumab-treated tumor vasculature. In summary,
a novel 12-mer peptide BRP selected using phage display techniques allowed non-invasive visualization of early responses to
anti-angiogenic treatment. Suitably labeled BRP peptide may be potentially useful pre-clinically and clinically for monitoring
treatment response. |
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