SUN-049 A NEAR-INFRARED PROBE FOR EARLY DIAGNOSIS OF ACUTE KIDNEY INJURY WITH DESIRABLE RENAL ABSORPTION

Abstract

Acute kidney injury (AKI) is common in patients. Delayed diagnosis and treatment of AKI due to the lack of efficient early diagnosis is an important cause for its high mortality. Numerous studies have shown that OONO- plays an important role in the pathological process of acute kidney injury. However, due to the extremely short lifetime (~10 ms) of ONOO- in physiological environment, it is impossible to separate the tissue and measure the species with conventional biology assays. In vivo near-infrared fluorescence imaging can realize the in situ and real-time analysis of elusive metabolites with high sensitivity. However, the noninasive fluorescence imaging of ONOO- in kidney has long been a challenge owing to the slow accumulation of conventional organic fluorophores in kidney but rapid accumulation in the skin which confers low signal-to-noise imaging contrast. we designed our renal absorption-based probe KNP-1, for high contrast fluorogenic imaging of ONOO− in kidney for early diagnosis of AKI. KNP-1 comprise two key building blocks : an ONOO− recognition functionality and a renal-absoption infrared-emission fluorophore. It is fluorescence-dark in the absence of ONOO− but can respond rapidly with ONOO− to produce strong fluorescences. KNP-1 exhibits excellent specificity, fast response, and high sensitivity toward ONOO− both in vitro and in vivo. In vivo fluorescent imaging of mice with probe KNP-1 realized the early diagnosis of AKI earlier than the clinically popular sCr and BUN methods. These results highlight ONOO- as a prodromal biomarker of AKI, and highlight the clinical promise of KNP-1 for early diagnosis of AKI.