abstract
- A new photoacoustic (PA) dye was developed as a simple-to-use reagent for creating targeted PA imaging agents. The lead molecule was prepared via an efficient two-step synthesis from an inexpensive commercially available starting material. With the dye's innate albumin-binding properties, the resulting tetrazine-derived dye is capable of localizing to tumor and exhibits a biological half-life of a few hours, allowing for an optimized distribution profile. The presence of tetrazine in turn makes it possible to link the albumin-binding optoacoustic signaling agent to a wide range of targeting molecules. To demonstrate the utility and ease of use of the platform, a novel PA probe for imaging calcium accretion was generated using a single-step bioorthogonal coupling reaction where high-resolution PA images of the knee joint in mice were obtained as early as 1 h post injection. Whole-body distribution was subsequently determined by labeling the probe with 99mTc and performing tissue counting following necropsy. These studies, along with tumor imaging and in vitro albumin binding studies, revealed that the core PA contrast agent can be imaged in vivo and can be easily linked to targeting molecules for organ-specific uptake.