Abstract
The emergence of PET probes for amyloid plaques and neurofibrillary tangles, hallmarks of Alzheimer disease (AD), enables monitoring of pathology in AD mouse models. However, small-animal PET imaging is limited by coarse spatial resolution. We have installed a custom-fabricated PET insert into our small-animal MRI instrument and used PET/MRI hybrid imaging to define regions of amyloid vulnerability in 5xFAD mice. We compared fluorine-18 [18F]-Florbetapir uptake in the 5xFAD brain by dedicated small-animal PET/MRI and PET/CT to validate the quantitative measurement of PET/MRI. Next, we used PET/MRI to define uptake in six brain regions. As expected, uptake was comparable to wild-type in the cerebellum and elevated in the cortex and hippocampus, regions implicated in AD. Interestingly, uptake was highest in the thalamus, a region often overlooked in AD studies. Development of small-animal PET/MRI enables tracking of brain region-specific pathology in mouse models, which may prove invaluable to understanding AD progression and therapeutic development.
Highlights
Alzheimer’s disease (AD), the most common form of dementia, is marked by the presence of extracellular amyloid plaques in the brain[1]
At least three radiofluorinated radiotracers, [18F]-Florbetapir15, [18F]-Florbetapen[16], and [18F]-Flutemetamol[17], have been developed; 18F has a physical half-life of 110 minutes, long enough for wide distribution from regional cyclotron facilities. [18F]-Florbetapir has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency for use in dementia patients
[18F]-Florbetapir has been used to analyze amyloid load and its spatial distribution in amyloid precursor protein (APP)/PS1-21 mice both ex vivo by autoradiography and in vivo by microPET. [18F]-FC119S (2-[2-(N-monomethyl)aminopyridine-6-yl]6-[(S)-3-fluoro-2-hydroxypropoxy]benzothazole) binds to Aβ in the APP/PS1 mouse model[21], pronounced localization was detected in the cortex, hippocampus and striatum[22]
Summary
PET/CT images were acquired using the Inveon microPET/microCT (Siemens Healthcare GmbH, Erlangen, Germany) dedicated high-resolution small-animal PET scanner. This system provides isotropic PET spatial resolution of 1.7 mm FWHM and absolute activity quantitation (e.g. in %ID/gm). PET/MR (work performed by MSKCC animal imaging core). Clinical PET processing electronics (Siemens Molecular Imaging, Knoxville, TN) are used to acquire data with high count rate performance. Https://www.sandersmedical.com/concordeMicro.htm) and the Inveon Research Workplace (IRW) software (Siemens Healthcare GmbH, Erlangen, Germany, https://www.siemens-healthineers.com/en-us/ molecular-imaging/preclinical-imaging/preclinicalglobal-support), which provides specialized 3D display and analysis capabilities Both ASIPro and IRW were purchased from Concorde Microsystems and Siemens Healthcare, respectively, and no permission is required. The coronally sectioned brains were used to quantify the cortex, hippocampus and caudate
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