Young Christina B, Vossler Hillary, Romero America, Smith Viktorija, Park Jennifer, Trelle Alexandra N, Winer Joseph R, Wilson Edward N, Zeineh Michael M, Sha Sharon J, Khalighi Mehdi, Yutsis Maya V, Morales Aimara P, Anders David, Zaharchuk Greg, Henderson Victor W, Andreasson Katrin I, Wagner Anthony D, Poston Kathleen L, Davidzon Guido A, Mormino Elizabeth C
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States.
Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States.
Imaging Neurosci (Camb). 2024 Oct 24;2. doi: 10.1162/imag_a_00329. eCollection 2024.
[18F]PI-2620 is a second generation tracer that has shown high binding affinity for tau aggregation in Alzheimer's disease (AD). However, [18F]PI-2620 signal in a large sample spanning the healthy aging and AD clinical spectrum as well as the stability of signal across different acquisition time windows has not yet been examined. Here, amyloid negative (Aβ-) cognitively unimpaired (CU; n = 49), amyloid positive (Aβ+) CU (n = 37), CU individuals with unknown amyloid status (n = 5), mild cognitive impairment (MCI; n = 14), dementia due to AD (n = 19), and non-AD neurodegenerative disorder (n = 54) participants were scanned with [18F]PI-2620 using a 45-75 min and/or 60-90 min acquisition time window. The impact of acquisition time on standardized uptake value ratio (SUVR) magnitude was first quantified with linear mixed models, and in participants and regions with high [18F]PI-2620 signal, SUVRs increased linearly up to 0.04 SUVR with each additional 5 min past injection time. We then accounted for differences in acquisition time using a voxel-wise correction approach and showed high correlations (alls ≥ 0.986) between SUVRs calculated from 45-75 min data and SUVRs from 60-90 min data that were interpolated to the 45-75 min scale in 15 participants who were scanned across both time windows. Using real and interpolated 45-75 min data, we next examined [18F]PI-2620 signal in Braak regions of interest and an off-target binding region (putamen) in Aβ- and Aβ+ CU, Aβ+ MCI, and Aβ+ AD dementia (n = 115) and showed that SUVRs in all Braak regions increased with greater disease severity. Within CU, higher Braak I SUVR was significantly associated with greater CSF pTau-181 (n = 35), and higher SUVRs were significantly associated with worse memory and language (n = 57). Thus, voxel-wise acquisition time corrections can be applied to combine [18F]PI-2620 datasets collected at different post-injection times, and once acquisition time is accounted for, [18F]PI-2620 signal shows the expected increases across the AD spectrum and can be used for detection of early tau elevations.
[18F]PI - 2620是一种第二代示踪剂，已显示出对阿尔茨海默病（AD）中tau蛋白聚集具有高结合亲和力。然而，在涵盖健康衰老和AD临床谱的大样本中[18F]PI - 2620信号以及不同采集时间窗内信号的稳定性尚未得到研究。在此，对淀粉样蛋白阴性（Aβ - ）认知未受损（CU；n = 49）、淀粉样蛋白阳性（Aβ + ）CU（n = 37）、淀粉样蛋白状态未知的CU个体（n = 5）、轻度认知障碍（MCI；n = 14）、AD所致痴呆（n = 19）以及非AD神经退行性疾病（n = 54）的参与者，使用45 - 75分钟和/或60 - 90分钟的采集时间窗进行[18F]PI - 2620扫描。首先用线性混合模型量化采集时间对标准化摄取值比率（SUVR）大小的影响，在具有高[18F]PI - 2620信号的参与者和区域中，注射时间每增加5分钟，SUVR线性增加至0.04 SUVR。然后我们使用体素级校正方法考虑采集时间的差异，并在15名在两个时间窗均进行扫描的参与者中显示，从45 - 75分钟数据计算的SUVR与内插至45 - 75分钟尺度的60 - 90分钟数据计算的SUVR之间具有高度相关性（所有r≥0.986）。接下来，使用真实的和内插的45 - 75分钟数据，我们在Aβ - 和Aβ + CU、Aβ + MCI以及Aβ + AD痴呆（n = 115）的Braak感兴趣区域和一个非靶标结合区域（壳核）中检查了[18F]PI - 2620信号，结果显示所有Braak区域的SUVR随疾病严重程度增加而升高。在CU个体中，较高的Braak I SUVR与较高的脑脊液pTau - 181显著相关（n = 35），较高的SUVR与较差的记忆和语言能力显著相关（n = 57）。因此，体素级采集时间校正可用于合并在不同注射后时间收集的[18F]PI - 2620数据集，并且一旦考虑了采集时间，[18F]PI - 2620信号在整个AD谱中显示出预期的升高，可用于检测早期tau蛋白升高。
