Evaluation of Dosimetry, Quantitative Methods, and Test-Retest Variability of 18F-PI-2620 PET for the Assessment of Tau Deposits in the Human Brain
Evaluation of Dosimetry, Quantitative Methods, and Test-Retest Variability of 18F-PI-2620 PET for the Assessment of Tau Deposits in the Human Brain
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DOI：
10.2967/jnumed.119.236240
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发表时间：
2020-06-01
影响因子：
9.3
通讯作者：
Stephens, Andrew W.
中科院分区：
文献类型：
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作者：
Bullich, Santiago;Barret, Olivier;Stephens, Andrew W.
F-18-PI-2620 是下一代 tau PET 示踪剂，已证明能够对可疑 tau 病理的空间分布进行成像。本研究的目的是评估 F-18-PI-2620 在人脑中的示踪剂生物分布、剂量测定和定量方法。研究了量化 tau 负载的完整动力学模型。针对全示踪剂动力学评估了无创动力学模型和半定量方法。最后，评估了测试和重新测试扫描的 PET 测量结果的再现性。方法：三名健康对照 (HC) 和 4 名阿尔茨海默病 (AD) 受试者接受了 2 次动态 PET 扫描，包括动脉采样。使用全示踪动力学（可逆 2 组织室 [2TC] 模型和 Logan 图形分析 [LGA]）和无创动力学模型（无创 LGA [NI-LGA] 和多线性参考组织模型 [MRTM2]）估计分布体积比 (DVR)。注射后在不同成像窗口测定SUV比率(SUVR)。评估了 DVR 和 SUVR 之间的相关性、效应大小（Cohen's d）和重测变异性（TRV）。此外，6名HC接受了1次示踪剂给药，并接受了全身PET以进行剂量测定计算。采用OLINDA 2.0计算器官剂量和全身有效剂量。结果：不同动力学模型之间以及 DVR(2TC) 和 SUVR 在 30 分钟至 90 分钟之间存在很强的相关性（R-2 > 0.97），R-2 大于 0.95。大多数地区和受试者在注射后 40 分钟左右达到长期平衡。不同区域的 SUVR 的 TRV 和效应大小在 30-60 分钟（TRV，3.8%；Cohen's d，3.80）、45-75 分钟（TRV，4.3%；Cohen's d，3.77）和 60-90 分钟（TRV，4.9%；Cohen's d，3.73）时相似，并在以后的时间点增加。通过肝胆和泌尿系统消除。成年女性全身有效剂量为33.3+/-2.1μSv/MBq，成年男性为33.1+/-1.4μSv/MBq，膀胱排尿间隔为1.5小时。结论：F-18-PI-2620 表现出快速动力学、合适的剂量测定和低 TRV。使用动脉采样的 2TC 模型测量的 DVR 与通过 NI-LGA、MRTM2 和 SUVR 测量的 DVR 密切相关。 SUVR 可用于 Tau 沉积物的 F-18-PI-2620 PET 定量，避免动脉血采样。注射后 45 至 75 分钟之间的静态 F-18-PI-2620 PET 扫描可提供出色的定量精度、较大的效应量和较低的 TRV。
F-18-PI-2620 is a next-generation tau PET tracer that has demonstrated ability to image the spatial distribution of suspected tau pathology. The objective of this study was to assess the tracer biodistribution, dosimetry, and quantitative methods of F-18-PI-2620 in the human brain. Full kinetic modeling to quantify tau load was investigated. Noninvasive kinetic modeling and semiquantitative methods were evaluated against the full tracer kinetics. Finally, the reproducibility of PET measurements from test and retest scans was assessed. Methods: Three healthy controls (HCs) and 4 Alzheimer disease (AD) subjects underwent 2 dynamic PET scans, including arterial sampling. Distribution volume ratio (DVR) was estimated using full tracer kinetics (reversible 2-tissue-compartment [2TC] model and Logan graphical analysis [LGA]) and noninvasive kinetic models (noninvasive LGA [NI-LGA] and the multilinear reference tissue model [MRTM2]). SUV ratio (SUVR) was determined at different imaging windows after injection. The correlation between DVR and SUVR, effect size (Cohen's d), and test-retest variability (TRV) were evaluated. Additionally, 6 HCs received 1 tracer administration and underwent whole-body PET for dosimetry calculation. Organ doses and the whole-body effective dose were calculated using OLINDA 2.0. Results: A strong correlation was found across different kinetic models (R-2 > 0.97) and between DVR(2TC) and SUVR between 30 and 90 min, with an R-2 of more than 0.95. Secular equilibrium was reached at around 40 min after injection in most regions and subjects. TRV and effect size for SUVR across different regions were similar at 30-60 min (TRV, 3.8%; Cohen's d, 3.80), 45-75 min (TRV, 4.3%; Cohen's d, 3.77) and 60-90 min (TRV, 4.9%; Cohen's d, 3.73) and increased at later time points. Elimination was via the hepatobiliary and urinary systems. The whole-body effective dose was 33.3 +/- 2.1 mu Sv/MBq for an adult female and 33.1 +/- 1.4 mu Sv/MBq for an adult male, with a 1.5-h urinary bladder voiding interval. Conclusion: F-18-PI-2620 exhibits fast kinetics, suitable dosimetry, and low TRV. DVR measured using the 2TC model with arterial sampling correlated strongly with DVR measured by NI-LGA, MRTM2, and SUVR. SUVR can be used for F-18-PI-2620 PET quantification of tau deposits, avoiding arterial blood sampling. Static F-18-PI-2620 PET scans between 45 and 75 min after injection provide excellent quantification accuracy, a large effect size, and low TRV.