The detection of beta-amyloid plaques in an Alzheimer's disease rat model with DDNP-SPIO

AIM: To detect the beta-amyloid plaques (A beta) in a rat model of Alzheimer's disease (AD) using superparamagnetic iron oxide nanoparticles coated with 1,1-dicyano-2-[6-(dimethylamino)-naphthalene-2-yl] propene carboxyl derivative (DDNP-SPIO). MATERIALS AND METHODS: DDNP-SPIO was prepared in a previous trial. The binding affinity of DDNP-SPIO to A beta was tested using fluorescence spectrophotometry in vitro. In vivo, five AD rats and five non-AD rats were intravenously injected with DDNP-SPIO at a dose of 76 mu mol Fe/kg. Coronal T-2(*)-weighted images were collected at baseline and repeated at 10, 30, and 60 min post-injection. Enhancement features of the two groups were analysed. After imaging, brain specimens were resected for Congo red and Prussian blue staining to assess the binding of DDNP-SPIO to A beta deposits. RESULTS: In vitro experiments indicated that the DDNP-SPIO nanoparticles displayed high binding affinities towards A beta with a K-d value of 29.4 nmo1/1. A significant decrease in SI was detected in the hippocampal area of AD rats after intravenous injection of the nanoparticles, but not in non-AD rats. The measurement of the percentage signal loss decreased to 52% in AD rats. In non-AD rats, only 10% signal loss was observed. There was a significant difference between the two groups (t = 4.533, p < 0.05). The signal decrease resulted from the binding of the DDNP-SPIO nanoparticles to the A beta plaques, which was identified with Congo red and Prussian blue staining. CONCLUSION: The DDNP-SPIO nanoparticles could potentially be used for visualizing A beta placlues, which may be helpful for diagnosing the early stages of AD and monitoring the effects of drug therapy. (C) 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.