人脑β-分泌酶 1 的 PET 成像：[F]PF-06684511 的辐射剂量学、定量分析和重复测试检查。
PET imaging of beta-secretase 1 in the human brain: radiation dosimetry, quantification, and test-retest examination of [F]PF-06684511.
机构信息
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden.
出版信息
Eur J Nucl Med Mol Imaging. 2020 Sep;47(10):2429-2439. doi: 10.1007/s00259-020-04739-5. Epub 2020 Mar 6.
PURPOSE
Beta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer's disease. [F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [F]PF-06684511 estimated in non-human primates was relatively high. This study was therefore designed to evaluate the whole-body distribution, dosimetry, quantification, and test-retest reliability of imaging brain BACE1 with [F]PF-06684511 in healthy volunteers.
METHODS
Five subjects were studied for the dosimetry study. Whole-body PET was performed for 366 min with 4 PET-CT sessions. Estimates of the absorbed radiation dose were calculated using the male adult model. Eight subjects participated in the test-retest study. Brain PET measurements were conducted for 123 min with an interval of 5 to 19 days between test and retest conditions. The total distribution volume (V) was estimated with one-tissue (1T), two-tissue (2T), compartment model (CM), and graphical analysis. Test-retest variability (TRV) and intraclass correlation coefficient (ICC) of V were calculated as reliability measures.
RESULTS
In the dosimetry study, the highest uptake was found in the liver (25.2 ± 2.3 %ID at 0.5 h) and the largest dose was observed in the pancreas (92.9 ± 52.2 μSv/MBq). The calculated ED was 24.7 ± 0.8 μSv/MBq. In the test-retest study, 2TCM described the time-activity curves well. V (2TCM) was the highest in the anterior cingulate cortex (6.28 ± 1.09 and 6.85 ± 0.81) and the lowest in the cerebellum (4.23 ± 0.88 and 4.20 ± 0.75). Mean TRV and ICC of V (2TCM) were 16.5% (12.4-20.5%) and 0.496 (0.291-0.644).
CONCLUSION
The ED of [F]PF-06684511 was similar to other F radioligands, allowing repeated PET measurements. 2TCM was the most appropriate quantification method. TRV of V was similar to other radioligands without a reference region, albeit with lower ICC. These data indicated that [F]PF-06684511 is a suitable radioligand to measure BACE1 level in the human brain.
TRIAL REGISTRATION
EudraCT 2016-001110-19 (registered 2016-08-08).
目的
β-分泌酶 1（BACE1）酶参与阿尔茨海默病的病理生理学。[F]PF-06684511 是一种正电子发射断层扫描（PET）示踪剂，用于成像 BACE1。尽管具有良好的脑动力学特性，但在非人类灵长类动物中估计的[F]PF-06684511 的有效剂量（ED）相对较高。因此，本研究旨在评估 [F]PF-06684511 在健康志愿者中成像大脑 BACE1 的全身分布、剂量学、定量和测试-重测可靠性。
方法
5 名受试者进行了剂量学研究。进行了 4 次 PET-CT 扫描，共进行了 366 分钟的全身 PET 扫描。使用男性成人模型计算估计的吸收辐射剂量。8 名受试者参加了测试-重测研究。在测试和重测条件之间间隔 5 至 19 天，进行了 123 分钟的脑 PET 测量。使用单组织（1T）、双组织（2T）、隔室模型（CM）和图形分析来估计总分布容积（V）。作为可靠性测量，计算了 V 的测试-重测变异性（TRV）和组内相关系数（ICC）。
结果
在剂量学研究中，肝脏的摄取最高（0.5 小时时为 25.2±2.3%ID），胰腺的剂量最大（92.9±52.2 μSv/MBq）。计算的 ED 为 24.7±0.8 μSv/MBq。在测试-重测研究中，2TCM 很好地描述了时间-活性曲线。前扣带回皮层（6.28±1.09 和 6.85±0.81）的 V（2TCM）最高，小脑（4.23±0.88 和 4.20±0.75）的 V（2TCM）最低。V（2TCM）的平均 TRV 和 ICC 分别为 16.5%（12.4-20.5%）和 0.496（0.291-0.644）。
结论
[F]PF-06684511 的 ED 与其他 F 示踪剂相似，允许重复 PET 测量。2TCM 是最合适的定量方法。V 的 TRV 与没有参考区域的其他示踪剂相似，尽管 ICC 较低。这些数据表明，[F]PF-06684511 是一种合适的示踪剂，可用于测量人类大脑中的 BACE1 水平。
试验注册
EudraCT 2016-001110-19（2016 年 8 月 8 日注册）。
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