Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging

Sadasivam, Pragalath; Fang, Xiaotian T.; Toyonaga, Takuya; Lee, Supum; Xu, Yuping; Zheng, Ming-Qiang; Spurrier, Joshua; Huang, Yiyun; Strittmatter, Stephen M.; Carson, Richard E.; Cai, Zhengxin

doi:10.1007/s11307-020-01567-9

Cited by 23 publications

(31 citation statements)

References 33 publications

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“…The kinetics of SV2A tracers, i.e., [ 11 C]UCB-J and [ 18 F]SynVesT-1, are known to be fit well with one-tissue compartment model based on the human and rhesus macaque data ( Finnema et al, 2016 ; Nabulsi et al, 2016 ; Li et al, 2019a ; Naganawa et al, 2021 ). For rodents, brain stem or cerebellum were used as a pseudo reference region to fit the other regional time activity curves ( Toyonaga et al, 2019 ; Sadasivam et al, 2020 ). As comparison, the Logan graphical analysis in wild-type mice showed that there was linear fit even at t * = 0 ( Sadasivam et al, 2020 ), which suggested that the tracer kinetics in rodent brain also can be described using one-tissue compartment model.…”

Section: Discussionmentioning

confidence: 99%

“…For rodents, brain stem or cerebellum were used as a pseudo reference region to fit the other regional time activity curves ( Toyonaga et al, 2019 ; Sadasivam et al, 2020 ). As comparison, the Logan graphical analysis in wild-type mice showed that there was linear fit even at t * = 0 ( Sadasivam et al, 2020 ), which suggested that the tracer kinetics in rodent brain also can be described using one-tissue compartment model. A key assumption of reference region analyses is that there should be no group or time differences of the tracer uptake in the reference region, in order to avoid bias.…”

Section: Discussionmentioning

confidence: 99%

“…The second generation SV2A PET tracers ([ 18 F]SynVesT-1, [ 18 F]SynVesT-2, and [ 18 F]SDM-16) possess higher specific binding in the brain. Of these tracers, [ 18 F]SynVesT-1 is the most advanced and has been evaluated in rodents ( Sadasivam et al, 2020 ), non-human primates ( Li et al, 2019a ), and healthy human subjects ( Li et al, 2021 ; Naganawa et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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PET Imaging of Synaptic Density: Challenges and Opportunities of Synaptic Vesicle Glycoprotein 2A PET in Small Animal Imaging

et al. 2022

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The development of novel PET imaging agents for synaptic vesicle glycoprotein 2A (SV2A) allowed for the in vivo detection of synaptic density changes, which are correlated with the progression and severity of a variety of neuropsychiatric diseases. While multiple ongoing clinical investigations using SV2A PET are expanding its applications rapidly, preclinical SV2A PET imaging in animal models is an integral component of the translation research and provides supporting and complementary information. Herein, we overview preclinical SV2A PET studies in animal models of neurodegenerative disorders and discuss the opportunities and practical challenges in small animal SV2A PET imaging. At the Yale PET Center, we have conducted SV2A PET imaging studies in animal models of multiple diseases and longitudinal SV2A PET allowed us to evaluate synaptic density dynamics in the brains of disease animal models and to assess pharmacological effects of novel interventions. In this article, we discuss key considerations when designing preclinical SV2A PET imaging studies and strategies for data analysis. Specifically, we compare the brain imaging characteristics of available SV2A tracers, i.e., [11C]UCB-J, [18F]SynVesT-1, [18F]SynVesT-2, and [18F]SDM-16, in rodent brains. We also discuss the limited spatial resolution of PET scanners for small brains and challenges of kinetic modeling. We then compare different injection routes and estimate the maximum throughput (i.e., number of animals) per radiotracer synthesis by taking into account the injectable volume for each injection method, injected mass, and radioactivity half-lives. In summary, this article provides a perspective for designing and analyzing SV2A PET imaging studies in small animals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PET Imaging of Synaptic Density: Challenges and Opportunities of Synaptic Vesicle Glycoprotein 2A PET in Small Animal Imaging

et al. 2022

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“…[ 18 F]SynVesT-1, [ 18 F]analog of [ 11 C]UCB-J, has demonstrated favourable in vivo brain uptake in non-human primate [106]. Sadasivam et al showed a lower [ 18 F]SynVesT-1 standard uptake value (SUV) across the whole brain of APP/PS1 mice compared to non-transgenic mice [107]. The results from a static (30-60 min post-injection) [ 18 F]SynVesT-1 PET scan was found comparable to kinetic modeling results [107].…”

Section: Cerebral Glucose Metabolism Imagingmentioning

confidence: 99%

“…[89] SV2A [ 11 C]UCB-J Striatal-lesioned rats [14,103,104] APP/PS1 mice [104] ArcSwe, Tg-L61 mice [105] [ 18 F]SynVesT-1 APP/PS1 mice [107] mGluR5 [ 18 F]FPEB 5×FAD mice [131,277] APP/PS1 mice [132] [ 11 C]ABP688 Tg-ArcSwe mice [133] 7nAChR IIa HDAC [ 18 F]TFAHA 3×Tg mice [278] GLP-1R [ 18 [ 11 C]tariquidar APP/PS1 mice [166] P-GP ABCB1…”

Section: Fundingmentioning

confidence: 99%

Positron Emission Tomography in Animal Models of Alzheimer’s Disease Amyloidosis

Ni¹

2021

Preprint

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Animal models of Alzheimer’s disease amyloidosis that recapitulate cerebral amyloid-beta pathology have been widely used in preclinical research, and have greatly enabled the mechanistic understanding of Alzheimer’s disease and the development of therapeutics. Comprehensive deep phenotyping of the pathophysiological and biochemical features in these animal models are essential. Recent advances in positron emission tomography have allowed the non-invasive visualization of the alterations in the brain of animal models as well as in patients with Alzheimer’s disease, These tools have facilitated our understanding of disease mechanisms, and provided longitudinal monitoring of treatment effect in animal models of Alzheimer’s disease amyloidosis. In this review, we focus on recent positron emission tomography studies of cerebral amyloid-beta accumulation, hypoglucose metabolism, synaptic and neurotransmitter receptor deficits (cholinergic and glutamatergic system), blood-brain barrier impairment and neuroinflammation (microgliosis and astrocytosis) in animal models of Alzheimer’s disease amyloidosis. We further propose the emerging targets and tracers for reflecting the pathophysiological changes, and discuss outstanding challenges in disease animal models and future outlook in on-chip characterization of imaging biomarkers towards clinical translation.

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APOE ε4 is associated with decreased synaptic density in cognitively impaired participants

He,

Li,

Wang

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONWe aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants.METHODSOne hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18F‐florbetapir and synaptic density PET with 18F‐SynVesT‐1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4‐associated synaptic density loss were analyzed.RESULTSCompared with non‐carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aβ) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype.DISCUSSIONThe APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.

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Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging

Cited by 23 publications

References 33 publications

PET Imaging of Synaptic Density: Challenges and Opportunities of Synaptic Vesicle Glycoprotein 2A PET in Small Animal Imaging

PET Imaging of Synaptic Density: Challenges and Opportunities of Synaptic Vesicle Glycoprotein 2A PET in Small Animal Imaging

Positron Emission Tomography in Animal Models of Alzheimer’s Disease Amyloidosis

APOE ε4 is associated with decreased synaptic density in cognitively impaired participants

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