Cystine knot peptides that bind alpha-V-beta-6 integrin

摘要

Disclosed are peptides comprising a molecular scaffold portion and a loop portion that binds to integrin α_vβ₆. This integrin is expressed on pancreatic tumors, making the peptides useful as imaging agents, among other uses. The peptides showed single-digit nanomolar dissociation constants similar to antibodies used clinically for imaging and therapy. The peptides rapidly accumulated in α_vβ₆-positive tumors, which led to excellent tumor-to-normal contrast. The peptides are specific for the targeted integrin α_vβ₆ receptors expressed on orthotopic pancreatic tumors and various xenografts used. Additionally, pharmacokinetic-stabilization strategies endowed knots with rapid renal clearance, which significantly reduced off-target dosing.