Fig. 1. Probe design.

(A) Schematic illustration of the development of dual Lys^Ald binding MRI probe for non-invasive detecting liver fibrogenesis. Chronic liver injury leads to the activation of stellate cells. In the remodeling of the extracellular matrix, closely separated Lys pairs on α1 chains of collagen telopeptide are oxidized by LOX to Lys^Ald. The dual hydrazine Gd³⁺ probe precisely targets these Lys^Ald pairs with high binding on-rate, high relaxivity upon binding and low off-rate, and results in increased dynamic range and noninvasive detection by MRI. (B) Chemical structures of Gd³⁺ complexes synthesized and studied in this work. (C) End-to-end distance distribution obtained from molecular dynamics simulation of the O-O distance between two α1–N⁹–Lys^Ald residues in type-I collagen and the N-N distance in piperazino-hydrazine groups in Gd-1,4 and Gd-1,7.