Alkaline Phosphatase Enabled Fluorogenic Reaction and in situ Coassembly of Near-Infrared and Radioactive Nanoparticles for in vivo Imaging

Smart near-infrared (NIR) fluorescence (FL) and positron emission tomography (PET) bimodal probes have shown promise for preoperative and intraoperative imaging of tumors. In this paper, we report an enzyme-activatable probe (P-CyFF- 68 Ga) and its cold probe (P-CyFF-Ga) using an enzyme-induced fluorogenic reaction and in situ coassembly strategy and demonstrate the utility for NIR FL/PET bimodality imaging of enzymatic activity. P-CyFF- 68 Ga and P-CyFF-Ga can be converted into dephosphorylated CyFF- 68 Ga and CyFF-Ga in response to alkaline phosphatase (ALP) and subsequently coassemble into fluorescent and radioactive nanoparticles (NP- 68 Ga). The ALP-triggered in situ formed NP- 68 Ga is prone to anchoring on the ALP-positive HeLa cell membrane, permitting the concurrent enrichment of NIR FL and radioactivity. The enhancements in NIR FL and radioactivity enables high sensitivity and deep-tissue imaging of ALP activity, consequently facilitating the delineation of HeLa tumor foci from the normal tissues in vivo .