In vivo detection of amyloid plaques in AD transgenic mice using gadolinium labeled ligands by MRI

Abstract

administration. Binding specificity to amyloid plaque was evaluated with tissue homogenates from the postmortem brain (frontal cortex and cerebellum) from Alzheimer’s patients and control subjects. The tissue homogenates were incubated in PBS and 0.1% fetal bovine serum with radiotracers for 15 min, centrifuged and bound radioactivity measured. Brain tissue sections were incubated with radiotracers, washed and exposed to Storage Phosphor Screens. Adjacent sections stained with Congo red. Results: The octanol-water partition coefficient (log PC) was in the range (1-3) optimum for blood brain barrier transport. The uptake of the compounds in the normal mouse brain was rapid and so was the clearance. Mouse brain uptake (%ID/g SD) at 2 min was 3.14 0.71 and 1.39 0.29 for CQ and HQ respectively and in 1 h decreased by 98%. Blood activity was 9.5 2.12 and 4.73 1.09 at 2 min for CQ and HQ respectively and decreased by 96% at 1 h. Practically no radioactivity was detectable in the brain and blood at 24 h for both the tracers. Activity in the frontal cortex of the human AD brain was 400-500% of the cerebellum and 300-400% of control cortex. Autoradiography showed the localization of the tracers in regions containing amyloid plaques recognized by Congo red. Nanoparticles enhanced the brain uptake by 15% compared to the free drug. Conclusions: Radioiodinated quinoline derivatives have rapid brain uptake and fast clearance from the normal brain and blood in mice. They showed binding specificity to amyloid deposits in AD brain homogenates. Plaque deposits were visualized by autoradiography. These studies warrant further evaluation of this class of molecules as amyloid imaging agents.