Direct Comparison of [18F]F-DPA with [18F]DPA-714 and [11C]PBR28 for Neuroinflammation Imaging in the same Alzheimer’s Disease Model Mice and Healthy Controls

López-Picón, Francisco R.; Keller, Thomas H.; Bocancea, Diana; Helin, Jatta S.; Krzyczmonik, Anna; Helin, Semi; Damont, Annelaure; Dollé, Frédéric; Rinne, Juha O.; Haaparanta‐Solin, Merja; Solin, Olof

doi:10.1007/s11307-021-01646-5

Cited by 12 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, we used the APP/PS1-21 transgenic (TG) mouse model of Aβ deposition, a reliable model to validate radiotracers in preclinical settings, which has been used in the development of novel PET radiotracers targeting reactive glia [ 26 , 27 ] and misfolded proteins, such as tau [ 28 ]. In this model, early onset Aβ plaques are associated with simultaneous and robust neuroinflammation, represented by the presence of increased reactive microglia around the Aβ plaques [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…The aim of the present study was to image reactive glia in the APP/PS1-21 TG mouse model of Aβ deposition longitudinally with [ 11 C]SMW139 targeting P2X7 receptor and compare tracer uptake in the same mice to that of [ 18 F]F-DPA targeting TSPO at the final imaging time point. In previous studies, [ 18 F]F-DPA targeting TSPO in the APP/PS1-21 mouse model has shown the ability to image reactive glia, differentiate transgenic from age-matched wild type mice, and superior brain uptake to the TSPO PET tracers [ 18 F]DPA-714 and [ 11 C] PBR28 [ 30 , 31 ]. This study contributes to the development of [ 11 C]SMW139 and [ 18 F]F-DPA for imaging reactive glia in the APP/PS1-21 mouse model.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glial reactivity in a mouse model of beta-amyloid deposition assessed by PET imaging of P2X7 receptor and TSPO using [11C]SMW139 and [18F]F-DPA

Alzghool,

Aarnio,

Helin

et al. 2024

EJNMMI Res

Self Cite

View full text Add to dashboard Cite

Background P2X7 receptor has emerged as a potentially superior PET imaging marker to TSPO, the gold standard for imaging glial reactivity. [11C]SMW139 is the most recently developed radiotracer to image P2X7 receptor. The aim of this study was to image reactive glia in the APP/PS1-21 transgenic (TG) mouse model of Aβ deposition longitudinally using [11C]SMW139 targeting P2X7 receptor and to compare tracer uptake to that of [18F]F-DPA targeting TSPO at the final imaging time point. TG and wild type (WT) mice underwent longitudinal in vivo PET imaging using [11C]SMW139 at 5, 8, 11, and 14 months, followed by [18F]F-DPA PET scan only at 14 months. In vivo imaging results were verified by ex vivo brain autoradiography, immunohistochemical staining, and analysis of [11C]SMW139 unmetabolized fraction in TG and WT mice. Results Longitudinal change in [11C]SMW139 standardized uptake values (SUVs) showed no statistically significant increase in the neocortex and hippocampus of TG or WT mice, which was consistent with findings from ex vivo brain autoradiography. Significantly higher [18F]F-DPA SUVs were observed in brain regions of TG compared to WT mice. Quantified P2X7-positive staining in the cortex and thalamus of TG mice showed a minor increase in receptor expression with ageing, while TSPO-positive staining in the same regions showed a more robust increase in expression in TG mice as they aged. [11C]SMW139 was rapidly metabolized in mice, with 33% of unmetabolized fraction in plasma and 29% in brain homogenates 30 min after injection. Conclusions [11C]SMW139, which has a lower affinity for the rodent P2X7 receptor than the human version of the receptor, was unable to image the low expression of P2X7 receptor in the APP/PS1-21 mouse model. Additionally, the rapid metabolism of [11C]SMW139 in mice and the presence of several brain-penetrating radiometabolites significantly impacted the analysis of in vivo PET signal of the tracer. Finally, [18F]F-DPA targeting TSPO was more suitable for imaging reactive glia and neuroinflammatory processes in the APP/PS1-21 mouse model, based on the findings presented in this study and previous studies with this mouse model.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glial reactivity in a mouse model of beta-amyloid deposition assessed by PET imaging of P2X7 receptor and TSPO using [11C]SMW139 and [18F]F-DPA

Alzghool,

Aarnio,

Helin

et al. 2024

EJNMMI Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…The 18-kDa translocator protein (TSPO)-binding radiotracers are the most widely used radiopharmaceuticals for imaging neuroinflammation; [ 11 C]PK11195 PET has been used to evaluate microglial response in fingolimod-treated MS patients . Its poor signal-to-noise ratio, high lipophilicity, and low blood–brain barrier penetration prevent the implementation of [ 11 C]PK11195 on clinical practice. , Consequently, a few second-generation PET radiotracers, such as [ 11 C]PBR28, [ 18 F]GE180, [ 18 F]DPA-714, and [ 18 F]F-DPA for imaging TSPO, have been reported. − Nevertheless, the Ala147Thr genotype polymorphism of TSPO influences the brain uptake of most of the TSPO radiotracers, resulting in the need for genetic prescreening to prevent high within-group variation, which creates substantial complexity for clinical studies. S1PR1 has gained significant interest since the approval of the S1PR modulators for the treatment of MS.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of S1PR1 Expression in the Postmortem Multiple Sclerosis Central Nervous System

Jiang,

Zhou,

Qiu

et al. 2023

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an immune-mediated disease that is characterized by demyelination and inflammation in the central nervous system (CNS). Previous studies demonstrated that sphingosine-1-phosphate receptor (S1PR) modulators effectively inhibit S1PR1 in immune cell trafficking and reduce entry of pathogenic cells into the CNS. Studies have also implicated a nonimmune, inflammatory role of S1PR1 within the CNS in MS. In this study, we explored the expression of S1PR1 in the development and progression of demyelinating pathology of MS by quantitative assessment of S1PR1 expression using our S1PR1-specific radioligand, [ 3 H]CS1P1, in the postmortem human CNS tissues including cortex, cerebellum, and spinal cord of MS cases and age-and sex-matched healthy cases. Immunohistochemistry with whole slide scanning for S1PR1 and various myelin proteins was also performed. Autoradiographic analysis using [ 3 H]CS1P1 showed that the expression of S1PR1 was statistically significantly elevated in lesions compared to nonlesion regions in the MS cases, as well as normal healthy controls. The uptake of [ 3 H]CS1P1 in the gray matter and nonlesion white matter did not significantly differ between healthy and MS CNS tissues. Saturation autoradiography analysis showed an increased binding affinity (K d ) of [ 3 H]CS1P1 to S1PR1 in both gray matter and white matter of MS brains compared to healthy brains. Our blocking study using NIBR-0213, a S1PR1 antagonist, indicated [ 3 H]CS1P1 is highly specific to S1PR1. Our findings demonstrated the activation of S1PR1 and an increased uptake of [ 3 H]CS1P1 in the lesions of MS CNS. In summary, our quantitative autoradiography analysis using [ 3 H]CS1P1 on human postmortem tissues shows the feasibility of novel imaging strategies for MS by targeting S1PR1.

show abstract

“…Studies have shown the presence of the rs6971 single nucleotide polymorphism (SNP) in TSPO , which produces different radioligand binding affinities (Owen et al, 2011 ; Tournier et al, 2020 ). Currently, TSPO is the primary target for PET and SPECT in vivo neuroinflammatory imaging to monitor the inflammatory state in the brain (Tournier et al, 2020 ; López-Picón et al, 2022 ). According to one of the hypotheses of AD pathogenesis, mitochondrial dysfunction occurs in the early stages, and thus, maintaining mitochondrial function may be a therapeutic strategy for AD (Readnower et al, 2011 ; Eckert et al, 2012 ; Kumar A. et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

Lai

Liu

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

Alzheimer's disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.

show abstract

Direct Comparison of [18F]F-DPA with [18F]DPA-714 and [11C]PBR28 for Neuroinflammation Imaging in the same Alzheimer’s Disease Model Mice and Healthy Controls

Cited by 12 publications

References 44 publications

Glial reactivity in a mouse model of beta-amyloid deposition assessed by PET imaging of P2X7 receptor and TSPO using [11C]SMW139 and [18F]F-DPA

Glial reactivity in a mouse model of beta-amyloid deposition assessed by PET imaging of P2X7 receptor and TSPO using [11C]SMW139 and [18F]F-DPA

Quantitative Analysis of S1PR1 Expression in the Postmortem Multiple Sclerosis Central Nervous System

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

Contact Info

Product

Resources

About