Abstract:
PURPOSE:Synapse loss is a hallmark of Alzheimer's disease (AD) and correlates with cognitive decline. The validation of a noninvasive in vivo imaging approach to quantify synapse would greatly facilitate our understanding of AD pathogenesis and assist drug developments for AD. As animal models of neurodegenerative and neuropsychiatric disorders play a critical role in the drug discovery and development process, a robust, objective, and translational method for quantifying therapeutic drug efficacy in animal models will facilitate the drug development process. In this study, we tested the quantification reliability of the SV2A PET tracer, [18F]SynVesT-1, in a mouse model of AD (APP/PS1) and wild-type controls, and developed a simplified quantification method to facilitate large cohort preclinical imaging studies. PROCEDURES:We generated nondisplaceable binding potential (BPND) and distribution volume ratio (DVR) values using the simplified reference tissue model (SRTM) on the 90-min dynamic PET imaging data, with brain stem and cerebellum as the reference region, respectively. Then, we correlated the standardized uptake value ratio (SUVR)-1 and SUVR averaged from different imaging windows with BPND and DVR, using brain stem and cerebellum as the reference region, respectively. We performed homologous competitive binding assay and autoradiographic saturation binding assay using [18F]SynVesT-1 to calculate the Bmax and Kd. RESULTS:Using brain stem as the reference region, the averaged SUVR-1 from 30 to 60 min postinjection correlated well with the BPND calculated using SRTM. Using cerebellum as the reference region, the averaged SUVR from 30 to 60 min postinjection correlated well with the SRTM DVR. From the homologous competitive binding assay and autoradiographic saturation binding assay, the calculated the Bmax and Kd were 4.5-18 pmol/mg protein and 9.8-19.6 nM, respectively, for rodent brain tissue. CONCLUSIONS:This simplified SUVR method provides reasonable SV2A measures in APP/PS1 mice and their littermate controls. Our data indicate that, in lieu of a full 90-min dynamic scan, a 30-min static PET scan (from 30 to 60 min postinjection) would be sufficient to provide quantification data on SV2A expression, equivalent to the data generated from kinetic modeling. The methods developed here are readily applicable to the evaluation of therapeutic effects of novel drugs in this rodent model using [18F]SynVesT-1 and small animal PET.
journal_name
Mol Imaging Bioljournal_title
Molecular imaging and biologyauthors
Sadasivam P,Fang XT,Toyonaga T,Lee S,Xu Y,Zheng MQ,Spurrier J,Huang Y,Strittmatter SM,Carson RE,Cai Zdoi
10.1007/s11307-020-01567-9subject
Has Abstractpub_date
2020-11-30 00:00:00eissn
1536-1632issn
1860-2002pii
10.1007/s11307-020-01567-9pub_type
杂志文章abstract:PURPOSE:Rats are important preclinical models for studying breast cancer metastasis and bone pathologies. In these research areas, fluorescence molecular tomography (FMT) is commonly applied for quantitative three-dimensional (3D) imaging in mice. However, uncertainties due to strong depth dependency of FMT signal and ...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-013-0698-8
更新日期:2014-06-01 00:00:00
abstract::This article is about head and neck tumor MR imaging and is not within the scope of two National Institutes of Health grants (R0ICA166171, ROICA228188) erroneously listed. Thus, the authors would like to remove the reference to the NIH grants R01CA166171 and R01CA228188 in this article. ...
journal_title:Molecular imaging and biology
pub_type: 已发布勘误
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journal_title:Molecular imaging and biology
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更新日期:2020-08-01 00:00:00
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更新日期:2006-09-01 00:00:00
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更新日期:2015-10-01 00:00:00
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更新日期:2020-06-01 00:00:00
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更新日期:2008-03-01 00:00:00
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doi:10.1007/s11307-016-1038-6
更新日期:2017-10-01 00:00:00
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更新日期:2018-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-01-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2012-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-10-01 00:00:00
abstract:PURPOSE:The tyrosine kinase receptor Axl is overexpressed in various types of cancer and correlated with cancer malignancy. Selective Axl blockade reduces tumor growth and metastasis. The purpose of this study was to examine whether the humanized anti-Axl antibody humanized 173 (h173) labeled with near-infrared fluores...
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pub_type: 杂志文章
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更新日期:2014-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11307-010-0394-x
更新日期:2011-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2014-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-04-01 00:00:00
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journal_title:Molecular imaging and biology
pub_type: 杂志文章,评审
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更新日期:2018-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-06-01 00:00:00