A Single-Chain Peptide Probe Targeting Pathological Collagen for Precise Staging of Hepatic Fibrosis by MR Imaging

Hepatic fibrosis, a chronic liver response to injury with potential severe outcomes like cirrhosis and liver cancer, necessitates urgent noninvasive diagnostic techniques to halt disease progression. We herein for the first time developed a single-chain peptide probe targeting pathological collagen for in vivo magnetic resonance imaging (MRI) of hepatic fibrosis. The novel (GhypO)₁₀ probe, distinguished by its unique monomeric conformation achieved through Pro to (2S,4S)-hydroxyproline (hyp) substitution and subsequent disruption of hydrogen bonding, exhibits selectivity for pathological collagen over its intact counterpart in connective tissues. Fluorescence imaging of liver specimens from fibrotic models displayed a discernible relationship between pathological collagen levels and fibrosis stage. Moreover, T1-weighted MR images post Gd-GhypO administration revealed progressive signal enhancement congruent with fibrosis severity, corroborated by a corresponding increase in the contrast-to-noise ratio (ΔCNR). Biodistribution analysis indicates that Gd-GhypO has low Gd retention in the main organs 24 h postinjection, ensuring the probe's safety for molecular imaging. The Gd-GhypO probe therefore emerges as a potent tool for the precise, noninvasive delineation of hepatic fibrosis stages, offering significant implications for the diagnosis and management of liver fibrosis.