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• W2166002290 abstract "Plaque depositions in Alzheimer's disease have been associated with elevated levels of transition metals (Zn, Cu). Previously we have reported the synthesis and preliminary evaluation of a small, blood brain barrier (BBB) permeating, [18 F] labeled quinoline ([18 F]HOQ). Here we report further evaluation of this agent in following the progression of the disease in AD (AAP/PS1) transgenic mice by PET imaging. High intensity CCD camera was used to study the interaction HOQ with Zn. Zn-HOQ complex (10 m L) was exposed to 290 nm LED. Zn ion was titrated with increasing amount of HOQ. [18 F]HOQ was prepared as previously reported by us. A b- Zn aggregates (100 nM) were incubated with increasing concentrations of [18 F]HOQ and bound activity measured. Frozen brain sections of AD and control (WT) mice were incubated with [18 F]HOQ, washed and exposed to Imaging Plate® for 2 h and images quantified as digital light units(DLU). Plaque density was measured by immunohistochemistry using NIH ImageJ software. AD and WT mice (n = 4 per group), (ages 4, 6 and 12 mo) were scanned in a Siemens Inveon® PET/CT scanner for 30 min immediately following the i.v. injection. SUV values for various regions of the brain were determined using AMIDE® software and an MRI mouse brain atlas. CCD light intensity was highest for Zn:ligand (2:1). [18 F]HOQ showed high binding affinity for A b- Zn aggregates (Kd = 1.5 nM). DLU correlated positively with plaque density. Integrated brain activity (by PET) over 10 min, for cortex, olfactory bulbs and hippocampus had higher values compared to cerebellum and were higher (P <0.05) in AD mice compared to WT at all ages. The values increased with age of AD mice and correlated to plaque density (R 2 = 0.88). The differences could be observed in mice as young as 4 months. [18 F]HOQ has high affinity for A b -Zn aggregates and its uptake correlated positively with plaque density. Brian uptake by PET increased with age in AD mice and correlated with plaque density. The differences were observed at an early age (4mo). [18 F]HOQ may be useful in monitoring the disease progression in AD mice and assessing the efficacy of therapeutic interventions." @default.
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• W2166002290 date "2012-07-01" @default.
• W2166002290 modified "2023-09-25" @default.
• W2166002290 title "P1-140: Assessment of disease progression in Alzheimer's transgenic mice by PET imaging with F-18 quinoline" @default.
• W2166002290 doi "https://doi.org/10.1016/j.jalz.2012.05.417" @default.
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