Exploring the origins of frequent tau-PET signal in vermal and adjacent regions

IF 8.6 1区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Agnes Kling, Julia Kusche-Palenga, Carla Palleis, Alexander Jäck, Alexander M. Bernhardt, Lukas Frontzkowski, Sebastian N. Roemer, Luna Slemann, Mirlind Zaganjori, Maximilian Scheifele, Lars Paeger, Gérard N. Bischof, Thilo van Eimeren, Alexander Drzezga, Osama Sabri, Michael Rullmann, Henryk Barthel, Johannes Levin, Jochen Herms, Nicolai Franzmeier, Günter Höglinger, Sigrun Roeber, Matthias Brendel, Johannes Gnörich
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引用次数: 0

Abstract

Purpose

Off-target binding remains a significant challenge in tau-PET neuroimaging. While off-targets including monoamine oxidase enzymes and neuromelanin-containing cells have been identified, recent studies indicated a relevant binding of novel tau tracers to melanin-containing structures. To date, little is known about the effect of melanocytes in the meninges on tracer signals in brain PET data. Thus, we aimed to identify the target structure causal for the frequently observed [18F]PI-2620 PET signal in the vermis and adjacent cerebellar regions.

Methods

274 participants underwent dynamic [18F]PI-2620 tau-PET: 3/4R-tauopathies (n = 85), 4R-tauopathies (n = 147), tau-negative disease controls (n = 24), and healthy controls (n = 18). Standardized uptake value ratio (SUVR) and kinetic parameters including the distribution volume ratio (DVR), tracer clearance (k2) and relative perfusion (R1), were compared among the cohorts and sexes using the Automated Anatomical Labelling (AAL) atlas. Age and p-Tau levels in cerebrospinal fluid (CSF) were assessed for their relationship with vermal tau-PET signal. Furthermore, we combined autoradiographic and histochemical experiments on post-mortem brain tissue of deceased patients (n = 9).

Results

Male participants revealed higher mean vermal [18F]PI-2620 DVR (0.95 ± 0.13; vs. females 0.88 ± 0.10, p < 0.0001). Sex-related differences were most pronounced in the 3/4R-tauopathy cohort (p < 0.0001). Mean SUVRVer/Cbl, k2 and correlation analyses of kinetic parameters did not differ among groups. Histological assessments revealed co-localization of leptomeningeal pigmented cells with strong autoradiography signal spots within the vermal fissures. Tau-related autoradiography signals, age or p-Tau levels did not correlate significantly with tau-PET signals. Iron deposits did not cause relevant autoradiography signals in the vermis.

Conclusion

Leptomeningeal melanocytes are the primary target structure for [18F]PI-2620 PET binding in anterior vermis, whereas iron and tau deposits do not contribute significantly.

探索疣状体和邻近区域频繁出现 tau-PET 信号的原因
目的脱靶结合在tau-PET神经成像中仍然是一个重大挑战。虽然已经确定了包括单胺氧化酶和含神经黑色素细胞在内的非靶标,但最近的研究表明,新型tau示踪剂与含黑色素结构的相关结合。迄今为止,人们对脑膜中的黑素细胞对脑PET数据中示踪信号的影响知之甚少。因此,我们旨在确定导致蚓部和邻近小脑区域频繁观察到的[18F]PI-2620 PET信号的目标结构。方法对274名受试者进行动态[18F]PI-2620 tau-PET: 3/4R-tauopathies (n = 85)、4R-tauopathies (n = 147)、tau阴性疾病对照(n = 24)和健康对照(n = 18)。标准化摄取值比(SUVR)和动力学参数,包括分布体积比(DVR)、示踪剂清除率(k2)和相对灌注(R1),使用自动解剖标记(AAL)图谱在队列和性别之间进行比较。评估年龄和脑脊液(CSF)中p-Tau水平与正常tau-PET信号的关系。此外,我们还对死亡患者的死后脑组织(n = 9)进行了放射自显影和组织化学实验。结果小型受试者的PI-2620 DVR平均值(0.95±0.13;女性0.88±0.10,p < 0.0001)。性别相关差异在3/4R-tauopathy队列中最为明显(p < 0.0001)。平均SUVRVer/Cbl、k2和动力学参数的相关分析各组间无差异。组织学检查显示薄脑膜色素细胞共定位,并伴有强烈的放射自显影信号点。tau相关放射自显影信号、年龄或p-Tau水平与tau-PET信号无显著相关性。铁沉积在蚓部没有引起相关的放射自显影信号。结论小脑膜黑素细胞是[18F]PI-2620 PET在前蚓结合的主要靶结构,而铁和tau沉积物的作用不显著。
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来源期刊
CiteScore
15.60
自引率
9.90%
发文量
392
审稿时长
3 months
期刊介绍: The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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