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 (vol 14, 25, 2024)

被引：0

作者：

Alzghool, Obada M. ^{[1
,2
,3
,4
]}

Aarnio, Richard ^{[1
,2
,3
]}

Helin, Jatta S. ^{[1
,2
]}

Wahlroos, Saara ^{[5
]}

Keller, Thomas ^{[5
]}

Matilainen, Markus ^{[4
]}

Solis, Junel ^{[6
,7
]}

Danon, Jonathan J. ^{[8
]}

Kassiou, Michael ^{[8
]}

Snellman, Anniina ^{[1
]}

Solin, Olof ^{[5
,9
,10
]}

Rinne, Juha O. ^{[4
,11
]}

Haaparanta-Solin, Merja ^{[1
,2
]}

机构：

[1] Univ Turku, Turku PET Ctr, PET Preclin Imaging Lab, Tykistokatu 6, Turku 20520, Finland

[2] Univ Turku, Med Res Lab, Tykistokatu 6, Turku 20520, Finland

[3] Univ Turku, Drug Res Doctoral Programme, Turku, Finland

[4] Turku Univ Hosp, Turku PET Ctr, Kiinamyllynkatu 4-8, Turku 20520, Finland

[5] Univ Turku, Turku PET Ctr, Radiopharmaceut Chem Lab, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland

[6] Abo Akad Univ, Turku BioImaging, Turku, Finland

[7] Univ Turku, Turku, Finland

[8] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

[9] Univ Turku, Dept Chem, Henrikinkatu 2, Turku 20500, Finland

[10] Abo Akad Univ, Turku PET Ctr, Accelerator Lab, Turku 20520, Finland

[11] Turku Univ Hosp, Dept Neurol, Kiinamyllynkatu 4-8, Turku 20520, Finland

来源：

EJNMMI RESEARCH | 2024年 / 14卷 / 01期

基金：

芬兰科学院;

关键词：

Alzheimer’s disease; APP/PS1-21; Microglia; P2X7; P2Y12; Positron emission tomography; TSPO; [!sup]11[!/sup]C]SMW139; [!sup]18[!/sup]F]F-DPA;

D O I：

10.1186/s13550-024-01103-8

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

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. © The Author(s) 2024.

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