Nanoparticulate radiolabelled quinolines detect amyloid plaques in mouse models of Alzheimer's disease.
Detecting aggregated amyloid peptides (Abeta 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 (125)I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) as in vivo probes. (125)I-CQ-PBCA NPs crossed the BBB (2.3 +/- 0.9 ID/g) (P < .05) in the WT mouse (N = 210), compared to (125)I-CQ (1.0 +/- 0.4 ID/g). (125)I-CQ-PBCA NP brain uptake increased in AD transgenic mice (APP/PS1) versus WT (N = 38; 2.54 x 10(5) +/- 5.31 x 10(4) DLU/mm(2); versus 1.98 x 10(5) +/- 2.22 x 10(4) DLU/mm(2)) and in APP/PS1/Tau. Brain increases were in mice intracranially injected with aggregated Abeta(42) peptide (N = 17; 7.19 x 10(5) +/- 1.25 x 10(5) DLU/mm(2)), versus WT (6.07 x 10(5) +/- 7.47 x 10(4) DLU/mm(2)). Storage phosphor imaging and histopathological staining of the plaques, Fe(2+) and Cu(2+), validated results. (125)I-CQ-PBCA NPs have specificity for Abeta in vitro and in vivo and are promising as in vivo SPECT ((123)I), or PET ((124)I) amyloid imaging agents.
Roney
Celeste A
CA
Division of Radiological Sciences, Department of Radiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Arora
Veera
V
Kulkarni
Padmakar V
PV
Antich
Peter P
PP
Bonte
Frederick J
FJ