Pharmacokinetically stabilized cystine knot peptides that bind alpha-v-beta-6 integrin with single-digit nanomolar affinities for detection of pancreatic cancer.

ABSTRACT:

Purpose

Detection of pancreatic cancer remains a high priority and effective diagnostic tools are needed for clinical applications. Many cancer cells overexpress integrin α(v)β(6), a cell surface receptor being evaluated as a novel clinical biomarker.

Experimental design

To validate this molecular target, several highly stable cystine knot peptides were engineered by directed evolution to bind specifically and with high affinity (3-6 nmol/L) to integrin α(v)β(6). The binders do not cross-react with related integrin α(v)β(5), integrin α(5)β(1), or tumor-angiogenesis-associated integrin, α(v)β(3).

Results

Positron emission tomography showed that these disulfide-stabilized peptides rapidly accumulate at tumors expressing integrin α(v)β(6). Clinically relevant tumor-to-mu

SUBMITTER: Kimura RH 

PROVIDER: S-EPMC3271184 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature