A novel clickable MSAP agent for dual fluorescence/nuclear labeling of biovectors

We herein describe the development of a novel dual-modality optical/radio-imaging agent for general and site-specific labeling of biovectors through a 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. The CBT-based multifunctional single-attachment-point (MSAP) agent enables a single-step synthesis of various dual-modality probes characterized by rapid conjugation, high labeling yields, metabolically stable products and applicability to orthogonal two-step labeling of sensitive biomolecules. In addition, the two-step radiolabeling protocol and click reaction were optimized by using CBT scavengers to improve the reaction rate and molar activity of the imaging probes. Our methodology allows for a simple and efficient synthetic route to produce a variety of dual-modality imaging agents for preoperative surgical planning and intraoperative surgical guidance.