Small-Molecule Absorber A1094 as a Stable and Fast-Clearing NIR-II Imaging Agent.

Photoacoustic imaging (PAI) in the second near-infrared window (NIR-II) is conducive to deep-tissue imaging due to small scattering coefficients, but often requires exogenous imaging agents. At present, nanoparticle-based NIR-II imaging agents are mainly used in non-clinical studies, some basic components of which are resistant to metabolism in vivo. The aim of this study was to examine the ∼600 Da croconaine absorber A1094, absorbing lights around 1094 nm, as a rare, small-molecule NIR-II imaging agent in vivo. The clinical translational potential of A1094 injection were systematically revealed, including sufficient solubility and freeness in blood, good anti-interference ability, and favourable pH/oxidation-reduction/metabolic stabilities. After intravenous administration of A1094 injection, PAI of murine ears exhibited comparable capillaries visibility to that of PAI with popular Au nanorods. The contrasts achieved with A1094 and Au nanorods were 1.78 and 1.29 times higher than before administration, in the healthy group, and 3.25 and 1.58 times higher in the inflammation group. Notably, A1094 demonstrated a desired faster liver clearance than Au nanorods. The PAI signal of A1094 was cleared by 74.2 % after 3 h, whereas Au nanorods were only cleared by 43.1 %. The main metabolic mechanisms of A1094 were identified as N-methylation and lipid hydrolysis by murine liver microsomes in vitro. Therefore, A1094 may have promising clinical potential as a stable and fast-clearing NIR-II imaging agent.