International Journal of Alzheimer's Disease (Jan 2009)
Nanoparticulate Radiolabelled Quinolines Detect Amyloid Plaques in Mouse Models of Alzheimer's Disease
Abstract
Detecting aggregated amyloid peptides (Aβ plaques) presents targets for developing biomarkers of Alzheimer's disease (AD). Polymeric n-butyl-2-cyanoacrylate (PBCA) nanoparticles (NPs) were encapsulated with radiolabelled amyloid affinity I125-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) as in vivo probes. I125-CQ-PBCA NPs crossed the BBB (2.3±0.9 ID/g) (P<.05) in the WT mouse (N = 210), compared to I125-CQ (1.0±0.4 ID/g). I125-CQ-PBCA NP brain uptake increased in AD transgenic mice (APP/PS1) versus WT (N = 38; 2.54×105±5.31×104 DLU/mm2; versus 1.98×105±2.22×104 DLU/mm2) and in APP/PS1/Tau. Brain increases were in mice intracranially injected with aggregated Aβ42 peptide (N = 17; 7.19×105±1.25×105 DLU/mm2), versus WT (6.07×105±7.47×104 DLU/mm2). Storage phosphor imaging and histopathological staining of the plaques, Fe2+ and Cu2+, validated results. I125-CQ-PBCA NPs have specificity for Aβ in vitro and in vivo and are promising as in vivo SPECT (I123), or PET (I124) amyloid imaging agents.