Brain Glucose Activated MRI Contrast Agent for Early Diagnosis of Alzheimer's Disease.

ABSTRACT

Brain glucose is an important biomarker of Alzheimer's disease (AD) and has a high specificity especially for early AD. Activatable magnetic resonance imaging (MRI) contrast agents (CAs) serve as a robust technology in the early diagnosis of many diseases; however, there is a lack of glucose-specific MRI CAs. To address this issue, in this work, we synthesized a novel MRI CA (ZIF-8/GOx@MnO2@PEG, ZGMP) that consists of porous zeolitic imidazolate framework-8 (ZIF-8) attached with glucose oxidase (GOx) and modified by MnO2 and PEG. The cascade reaction of brain glucose with ZGMP could result in the production of Mn(II) and an enhanced MRI signal. An early AD mouse model was constructed through injection of the Aß42 oligomer into the parenchyma of mice and utilized to verify the brain glucose activated MRI of ZGMP. The results indicated a higher glucose uptake in early AD mice compared to that in normal mice, with an obviously enhanced T1WI at the region of interest. This work gets rid of the need for a specific scanning sequence for glucose MRI, paving a convenient way for MRI diagnosis of early AD.