The novel tau-PET tracer [¹⁸F]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 [¹⁸F]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. [¹⁸F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [¹⁸F]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_30-60) 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_SRTM: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2_SRTM: 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_30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope_9-60: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [¹⁸F]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.

新型 tau-PET 示踪剂 [ ¹⁸ F]PI-2620 可检测 3/4-重复-(R)-tauopathy 阿尔茨海默病 (AD) 和 4R-tauopathies corticobasal 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[ ^{18 F]PI-2620 结合特征是否区分3/4R-和4R-tau蛋白病。}评估了 10 名患有 3/4R tauopathy (AD 连续体) 的患者和 29 名患有 4R tauopathy (CBS, PSP) 的患者。[ ¹⁸ F]PI-2620 PET 扫描在 0-60 分钟 pi 获得，并计算分布体积比 (DVR)。[ ¹⁸F]PI-2620 阳性簇（DVR ≥ 2.5 SD 与 11 名健康对照）通过无创动力学建模进行评估。比较了 R1（递送）、k2 和 k2a（流出）、DVR、30-60 分钟标准化摄取值比（SUVR _30-60）和灌注后阶段 SUVR（9-60 分钟 pi）的线性斜率介于 3/4R-和 4R-tau蛋白病之间。4R-tau 病例的皮质簇表明更高的递送（R1 _SRTM：0.92 ± 0.21 vs. 0.83 ± 0.10，p = 0.0007），更高的流出（k2 _SRTM：0.17/min ±0.21/min vs. 0.06/min ± 0.07/min , p < 0.0001), 较低的 DVR (1.1 ± 0.1 vs. 1.4 ± 0.2, p < 0.0001), 较低的 SUVR _30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) 和更平坦的灌注后斜率相位（斜率_9-60: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) 与 3/4R-tau 情况相比。[ ¹⁸ F]PI-2620 在皮质区域的结合特征区分 3/4R-和 4R-tau蛋白病。与 3/4R-tau 蛋白病相比，较高的示踪剂清除率表明 4R tau蛋白病的结合稳定性较差。