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 (18)F-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.