PET Imaging of a Transgenic Tau Rat Model SHR24 with [¹⁸F]AV1451.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-01-21 DOI:10.1007/s11307-024-01972-4

Nisha K Ramakrishnan, Annie Ziyi Zhao, Stephen Thompson, Selena Milicevic Sephton, David J Williamson, Tomáš Smolek, Norbert Žilka, Franklin I Aigbirhio

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引用次数: 0

Abstract

Purpose: Positron Emission Tomography (PET) scans with radioligands targeting tau neurofibrillary tangles (NFT) have accelerated our understanding of the role of misfolded tau in neurodegeneration. While intended for human research, applying these radioligands to small animals establishes a vital translational link. Transgenic animal models of dementia, such as the tau rat SHR24, play a crucial role in enhancing our understanding of these disorders. This study aims to evaluate the utility of SHR24 rat model for PET studies.

Procedures: Dynamic PET scans were conducted in male SHR24 rats and their wild-type SHR (SHRwt) littermates using [¹⁸F]AV1451. Rapid blood sampling and metabolite analysis were performed to acquire input curves. Time activity curves were obtained from various brain regions over 60 min. Blood-based, 2-Tissue Compartment Model (2-TCM) and Logan graphical analysis were used to obtain kinetic modelling parameters. The ability of reference tissue models to predict the binding potential (BP_ND) were assessed. Autoradiography studies were performed to corroborate the scan data.

Results: Total distribution volume (V_T) was the best predicted parameter which revealed significantly higher uptake of [¹⁸F]AV1451 in the cortex (5.8 ± 1.1 vs 4.6 ± 0.7, P < 0.05) of SHR24 rats compared to SHRwt rats. Binding potential obtained from 2-TCM was variable, however BP_ND from reference tissue models detected significantly higher binding in cortex (0.28 ± 0.07 vs 0.20 ± 0.04, P < 0.01 by SRTM) and brainstem (0.14 ± 0.04 vs 0.08 ± 0.02, P < 0.01, by SRTM).

Conclusions: With the ability to detect binding of established radioligand [¹⁸F]AV1451 in these rats, we have demonstrated the utility of this model for assessing aggregated tau neurobiology by PET, with reference tissue models providing potential for longitudinal studies.

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[18F]AV1451转基因Tau大鼠模型SHR24的PET显像

目的：针对tau神经原纤维缠结（NFT）的放射性配体正电子发射断层扫描（PET）加速了我们对错误折叠tau在神经变性中的作用的理解。虽然用于人类研究，但将这些放射性配体应用于小动物身上建立了重要的转化联系。痴呆的转基因动物模型，如tau鼠SHR24，在增强我们对这些疾病的理解方面发挥着至关重要的作用。本研究旨在评价SHR24大鼠模型在PET研究中的实用性。方法：采用[18F]AV1451对雄性SHR24大鼠及其野生型SHR （SHRwt）仔鼠进行动态PET扫描。快速采血和代谢物分析获得输入曲线。在60分钟内获得脑各区域的时间活动曲线。基于血液，2-组织室模型（2-TCM）和Logan图形分析获得动力学建模参数。评估了参考组织模型预测结合电位（BPND）的能力。进行放射自显影研究以证实扫描数据。结果：总分布体积（VT）是最佳预测参数，显示[18F]AV1451在皮质的摄取显著增加（5.8±1.1 vs 4.6±0.7），参考组织模型的P ND在皮质的结合显著增加（0.28±0.07 vs 0.20±0.04，P）。由于能够在这些大鼠中检测到已建立的放射性配体[18F]AV1451的结合，我们已经证明了该模型在PET评估聚集tau神经生物学方面的实用性，参考组织模型为纵向研究提供了潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.