Renal-Clearable Molecular Reporters for Near-Infrared Fluorescence Imaging and Urinalysis of Pulmonary Metastatic Tumor.

Despite approximately 40% of all patients with cancer developing pulmonary metastases in the course of their disease, it remains a diagnostic challenge in clinical practice. Herein, we propose a fluorogenic probe (CPRG) with gamma-glutamyl transferase (GGT)-triggered signal turn-on for near-infrared fluorescence imaging (NIRF) and urinalysis of orthotopic pulmonary metastatic tumors in living mice. CPRG comprised four key moieties: a GGT-reactive moiety, a hemicyanine-based signal unit, a polyethylene glycol linker, and an active tumor targeting moiety. Such a tailored probe is intrinsically nonfluorescent and only activates its NIRF signals in the presence of GGT. After intratracheal administration into the lungs of living tumor-bearing mice, CPRG can efficiently accumulate in the pulmonary tumors and sensitively turn-on the NIRF signal for real-time imaging. Relying on the high renal clearance efficiency (∼70% ID), it can be rapidly excreted through kidneys for urinalysis and assessed by the chemotherapeutic efficacy of cisplatin. This study not only reports fluorogenic tracers for imaging of pulmonary metastatic tumors but also provides guidelines for the development of molecular probes for companion diagnosis of metastatic cancer.