Kropholler Marc A, Boellaard Ronald, Schuitemaker Alie, van Berckel Bart N M, Luurtsema Gert, Windhorst Albert D, Lammertsma Adriaan A
Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands.
J Cereb Blood Flow Metab. 2005 Jul;25(7):842-51. doi: 10.1038/sj.jcbfm.9600092.
(R)-[(11)C]PK11195 ([1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[(11)C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K(1)/k(2) ratio, k(4) or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[(11)C]PK11195 PET brain studies. Simulations showed that fixing the K(1)/k(2) ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K(1)/k(2) fixed to whole cortex value is optimal for analyzing (R)-[(11)C]PK11195 PET brain studies.
（R）-[（11）C]PK11195（[1-（2-氯苯基）-N-甲基-N-（1-甲基丙基）-3-异喹啉甲酰胺]）是外周苯二氮䓬受体的配体，该受体在大脑中主要表达于活化的小胶质细胞上。本研究旨在通过临床研究和蒙特卡罗模拟，确定哪种示踪剂动力学血浆输入模型能最好地描述（R）-[（11）C]PK11195的动力学。对13名受试者进行了动态正电子发射断层扫描（PET），同时在线监测动脉血中的放射性。采集离散血样以生成代谢物校正后的血浆输入函数。将单组织、双组织不可逆和双组织可逆房室模型，在固定和不固定K（1）/k（2）比值、k（4）或血容量至全皮质值的情况下，与数据进行拟合。通过在生理范围内改变参数，并使用蒙特卡罗模拟确定结合潜力和分布容积的准确性和可重复性，研究了将参数固定为不正确值的影响。临床数据表明，双组织可逆房室模型最适合分析（R）-[（11）C]PK11195的PET脑研究。模拟表明，固定该模型的K（1）/k（2）比值可在准确性和可重复性之间实现最佳权衡。得出的结论是，将K（1）/k（2）固定为全皮质值的双组织可逆房室模型最适合分析（R）-[（11）C]PK11195的PET脑研究。
