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[F]PI-2620 的结合特性通过 PET 区分了不同 tau 病中的临床预测 tau 同工型。

Binding characteristics of [F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET.

机构信息

Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.

Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.

出版信息

J Cereb Blood Flow Metab. 2021 Nov;41(11):2957-2972. doi: 10.1177/0271678X211018904. Epub 2021 May 27.

DOI:10.1177/0271678X211018904
PMID:34044665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8545042/
Abstract

The novel tau-PET tracer [F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer's disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [F]PI-2620-positive clusters (DVR ≥ 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2: 0.17/min ±0.21/min vs. 0.06/min ± 0.07/min, p < 0.0001), lower DVR (1.1 ± 0.1 vs. 1.4 ± 0.2, p < 0.0001), lower SUVR (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [F]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies.

摘要

新型 Tau-PET 示踪剂 [F]PI-2620 可检测 3/4 重复-(R)-tau 病变阿尔茨海默病 (AD) 和 4R-tau 病变皮质基底节综合征 (CBS) 和进行性核上性麻痹 (PSP)。我们确定了源自非侵入性参考组织建模的 [F]PI-2620 结合特征是否可区分 3/4R- 和 4R-tau 病变。评估了 10 名 3/4R tau 病变患者 (AD 连续体) 和 29 名 4R tau 病变患者 (CBS、PSP)。[F]PI-2620 PET 扫描在注射后 0-60 分钟内采集，计算分布容积比 (DVR)。通过非侵入性动力学建模评估 [F]PI-2620 阳性簇 (DVR≥2.5 SD 与 11 名健康对照)。比较了 3/4R-和 4R-tau 病变之间的 R1(输送)、k2 和 k2a(流出)、DVR、30-60 分钟标准化摄取值比 (SUVR)以及灌注后 SUVR 的线性斜率 (9-60 分钟 p.i.)。4R-tau 病例的皮质簇显示输送更高 (R1：0.92±0.21 与 0.83±0.10，p=0.0007)、流出更高 (k2：0.17/min±0.21/min 与 0.06/min±0.07/min，p<0.0001)、DVR 更低 (1.1±0.1 与 1.4±0.2，p<0.0001)、SUVR 更低 (1.3±0.2 与 1.8±0.3，p<0.0001)，灌注后 SUVR 的斜率更平坦 (斜率：0.006/min±0.007/min 与 0.016/min±0.008/min，p<0.0001)与 3/4R-tau 病例相比。[F]PI-2620 在皮质区域的结合特征可区分 3/4R-和 4R-tau 病变。与 3/4R-tau 病变相比，4R-tau 病变中示踪剂清除率较高表明结合更不稳定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/9533c10fc321/10.1177_0271678X211018904-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/e799761777c4/10.1177_0271678X211018904-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/09b9783e9fbb/10.1177_0271678X211018904-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/8beca211721a/10.1177_0271678X211018904-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/9533c10fc321/10.1177_0271678X211018904-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/e799761777c4/10.1177_0271678X211018904-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/09b9783e9fbb/10.1177_0271678X211018904-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/8beca211721a/10.1177_0271678X211018904-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e97/8756464/9533c10fc321/10.1177_0271678X211018904-fig4.jpg

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