Xanthene‐Based Dyes for Photoacoustic Imaging and their Use as Analyte‐Responsive Probes

Abstract Developing imaging tools that can report on the presence of disease‐relevant analytes in multicellular organisms can provide insight into fundamental disease mechanisms as well as provide diagnostic tools for the clinic. Photoacoustic imaging (PAI) is a light‐in, sound‐out imaging technique that allows for high resolution, deep‐tissue imaging with applications in pre‐clinical and point‐of‐care settings. The continued development of near‐infrared (NIR) absorbing small‐molecule dyes promises to improve the capabilities of this emerging imaging modality. For example, new dye scaffolds bearing chemoselective functionalities are enabling the detection and quantification of disease‐relevant analytes through activity‐based sensing (ABS) approaches. Recently described strategies to engineer NIR absorbing xanthenes have enabled development of analyte‐responsive PAI probes using this classic dye scaffold. Herein, we present current strategies for red‐shifting the spectral properties of xanthenes via bridging heteroatom or auxochrome modifications. Additionally, we explore how these strategies, coupled with chemoselective spiroring‐opening approaches, have been employed to create ABS probes for in vivo detection of hypochlorous acid, nitric oxide, copper (II), human NAD(P)H: quinone oxidoreductase isozyme 1, and carbon monoxide. Given the versatility of the xanthene scaffold, we anticipate continued growth and development of analyte‐responsive PAI imaging probes based on this dye class.