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J Nucl Med. 2012; 53 (Supplement 1):1886
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Neurosciences

MTA II: Basic Science (Neurosciences) Posters

PET imaging of AD transgenic mice at an early age with 18F-labeled hydroxyquinoline

Padmakar Kulkarni1, Mustafa Alhasan1, Nikolai Slavine1, Srinivas Chiguru1, Guiyang Hao1, N. Vasdev2, Patrick Thomas1, Xiankai Sun1, P. Antich1 and Frederick Bonte1

1 Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 2 Nuclear Medicine, Massachusetts General Hospital, Boston, MA

Abstract No. 1886

Objectives: To evaluate [18F]2-fluoro-8-hydroxyquinoline( [18F]HOQ) for its in vitro binding properties to Zn, Aβ-Zn aggregates and PET imaging of plaques in AD (APP/PS1) transgenic mice at an early age.

Methods: High sensitivity CCD camera was used to study interaction of 2-F HOQ with Zn as conventional methods were not suitable. Complex (10 μL) placed on a quartz slide was exposed to 290 nm LED. Zn ion was titrated with increasing amount of 2-F HOQ. Aβ-Zn aggregates (100 nM) were incubated with increasing concentrations of [18F]HOQ for 30 min and activity bound to the aggregates was measured. Frozen brain sections of AD and control (WT) mice were incubated with [18F]HOQ (50 μCi/mL), washed and exposed to Phosphor 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 minutes immediately following i.v. injection. SUV values for various brain regions were determined using AMIDE® software and an MRI 3D mouse brain atlas.

Results: Liight intensity was highest for Zn:ligand (1:2) and reduced to background level on addition of EDTA. [18F]HOQ showed high binding affinity for Aβ-Zn (Kd=1.5 nM). DLU correlated with plaque density. Integrated brain activity 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 [R2=0.88]. The differences could be observed in mice as young as 4 months.

Conclusions: 2-F HOQ forms 2:1 complex with Zn. [18F]HOQ has high affinity for Aβ-Zn aggregates. Brain uptake by PET correlated with plaque density and differences were observed beginning at 4 months. [18F]HOQ may be useful in monitoring the disease progression in AD animal models and in assessing the efficacy of therapeutic agents.

Research Support: Worsham Fund and NIH (NIA) Grant# 1RC1AG0330





This Article
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Right arrow Articles by Kulkarni, P.
Right arrow Articles by Bonte, F.