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An optically labeled peptide rapidly and specifically bound the claudin-1 membrane protein, a “promising” target for early detection of human colonic adenomas, in a study published in the March issue of Cellular and Molecular Gastroenterology and Hepatology.
If the peptide holds up in human studies, it could be used to screen high-risk patients with multiple polyps, inflammatory bowel disease, Lynch syndrome, or a family history of (CRC), said Dr. Emily Rabinsky and associates at the University of Michigan, Ann Arbor. Peptides can be delivered topically to mucosa in high concentrations to maximize binding and image contrast while minimizing the risk of systemic absorption and toxicity, they added.
Adenomatous polyps express early molecular targets that are candidates for enhanced CRC surveillance. More than 35% of premalignant colonic lesions are flat and therefore difficult to visualize, so up to 25% of adenomas are missed during typical white light colonoscopy. Premalignant adenomas cannot be distinguished grossly from noncancerous hyperplastic polyps (Cell Mol Gastroenterol Hepatol. 2016. doi: 10.1016/j.jcmgh.2015.12.001).
The researchers used gene expression data to confirm that claudin-1 is an early target in colonic adenomas, and performed phage display against the extracellular loop of claudin-1 to identify the claudin-1-specific RTSPSSR peptide. After labeling the peptide with Cy5.5, they characterized its binding parameters and confirmed that it specifically binds to human CRC cells. They did in vivo fluorescent colonic endoscopy of CPC;Apc mice, which spontaneously develop colonic adenomas. They used immunofluorescence to confirm that RTSPSSR binds specifically to adenomas from the proximal human colon.
Claudin-1 expression was 2.5 times greater in human colonic adenomas than normal colonic mucosa, and the RTSPSSR peptide specifically bound claudin-1 in knockdown and competition studies. Binding to CRC cells occurred in 1.2 minutes, with an “adequate” affinity of 42 nmol/L. The peptide specifically bound to both flat and polyploid murine colonic adenomas, with a significantly higher target-to-background ratio compared with normal in vivo images.
The National Institutes of Health and Mary L. Petrovich provided funding. Dr. Rabinsky and two coauthors are coinventors on a provisional patent on the claudin-1 peptide.
An optically labeled peptide rapidly and specifically bound the claudin-1 membrane protein, a “promising” target for early detection of human colonic adenomas, in a study published in the March issue of Cellular and Molecular Gastroenterology and Hepatology.
If the peptide holds up in human studies, it could be used to screen high-risk patients with multiple polyps, inflammatory bowel disease, Lynch syndrome, or a family history of (CRC), said Dr. Emily Rabinsky and associates at the University of Michigan, Ann Arbor. Peptides can be delivered topically to mucosa in high concentrations to maximize binding and image contrast while minimizing the risk of systemic absorption and toxicity, they added.
Adenomatous polyps express early molecular targets that are candidates for enhanced CRC surveillance. More than 35% of premalignant colonic lesions are flat and therefore difficult to visualize, so up to 25% of adenomas are missed during typical white light colonoscopy. Premalignant adenomas cannot be distinguished grossly from noncancerous hyperplastic polyps (Cell Mol Gastroenterol Hepatol. 2016. doi: 10.1016/j.jcmgh.2015.12.001).
The researchers used gene expression data to confirm that claudin-1 is an early target in colonic adenomas, and performed phage display against the extracellular loop of claudin-1 to identify the claudin-1-specific RTSPSSR peptide. After labeling the peptide with Cy5.5, they characterized its binding parameters and confirmed that it specifically binds to human CRC cells. They did in vivo fluorescent colonic endoscopy of CPC;Apc mice, which spontaneously develop colonic adenomas. They used immunofluorescence to confirm that RTSPSSR binds specifically to adenomas from the proximal human colon.
Claudin-1 expression was 2.5 times greater in human colonic adenomas than normal colonic mucosa, and the RTSPSSR peptide specifically bound claudin-1 in knockdown and competition studies. Binding to CRC cells occurred in 1.2 minutes, with an “adequate” affinity of 42 nmol/L. The peptide specifically bound to both flat and polyploid murine colonic adenomas, with a significantly higher target-to-background ratio compared with normal in vivo images.
The National Institutes of Health and Mary L. Petrovich provided funding. Dr. Rabinsky and two coauthors are coinventors on a provisional patent on the claudin-1 peptide.
An optically labeled peptide rapidly and specifically bound the claudin-1 membrane protein, a “promising” target for early detection of human colonic adenomas, in a study published in the March issue of Cellular and Molecular Gastroenterology and Hepatology.
If the peptide holds up in human studies, it could be used to screen high-risk patients with multiple polyps, inflammatory bowel disease, Lynch syndrome, or a family history of (CRC), said Dr. Emily Rabinsky and associates at the University of Michigan, Ann Arbor. Peptides can be delivered topically to mucosa in high concentrations to maximize binding and image contrast while minimizing the risk of systemic absorption and toxicity, they added.
Adenomatous polyps express early molecular targets that are candidates for enhanced CRC surveillance. More than 35% of premalignant colonic lesions are flat and therefore difficult to visualize, so up to 25% of adenomas are missed during typical white light colonoscopy. Premalignant adenomas cannot be distinguished grossly from noncancerous hyperplastic polyps (Cell Mol Gastroenterol Hepatol. 2016. doi: 10.1016/j.jcmgh.2015.12.001).
The researchers used gene expression data to confirm that claudin-1 is an early target in colonic adenomas, and performed phage display against the extracellular loop of claudin-1 to identify the claudin-1-specific RTSPSSR peptide. After labeling the peptide with Cy5.5, they characterized its binding parameters and confirmed that it specifically binds to human CRC cells. They did in vivo fluorescent colonic endoscopy of CPC;Apc mice, which spontaneously develop colonic adenomas. They used immunofluorescence to confirm that RTSPSSR binds specifically to adenomas from the proximal human colon.
Claudin-1 expression was 2.5 times greater in human colonic adenomas than normal colonic mucosa, and the RTSPSSR peptide specifically bound claudin-1 in knockdown and competition studies. Binding to CRC cells occurred in 1.2 minutes, with an “adequate” affinity of 42 nmol/L. The peptide specifically bound to both flat and polyploid murine colonic adenomas, with a significantly higher target-to-background ratio compared with normal in vivo images.
The National Institutes of Health and Mary L. Petrovich provided funding. Dr. Rabinsky and two coauthors are coinventors on a provisional patent on the claudin-1 peptide.