Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
J Nucl Med. 2014 Dec;55(12):1966-72. doi: 10.2967/jnumed.114.143727. Epub 2014 Nov 13.
This study provides the first comprehensive quantification of translocator protein (TSPO) binding using SPECT and 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide ((123)I-CLINDE) in neurologic patients. (123)I-CLINDE is structurally related to well-known PET ligands such as (18)F-PBR111 and (18)F-DPA-714.
Six patients with cerebral stroke and 4 patients with glioblastoma multiforme (GBM) underwent 150-min dynamic SPECT scans with arterial blood sampling. Four of the patients were rescanned. All patients were genotyped for the rs6971 polymorphism. Volumes of interest were delineated on the individual SPECT scans and the coregistered MR images. Compartmental and graphical models using arterial input or the cerebellum as a reference region were used to quantify (123)I-CLINDE binding.
Among the 6 models investigated, the 2-tissue-compartment model with arterial input described the time-activity data best. Time-stability analyses suggested that acquisition time should be at least 90 min. Intersubject variation in the cerebellar distribution volume (VT) was clearly related to the TSPO genotype. In the stroke patients the VT in the periinfarction zone, compared with VT in the ipsilateral cerebellum, ranged from 1.4 to 3.4, and in the GBM patients the VT in the tumor, compared with the VT in the cerebellum, ranged from 1.8 to 3.4. In areas of gadolinium extravasation, (123)I-CLINDE binding parameters were not significantly changed. Thus, (123)I-CLINDE binding does not appear to be importantly affected by blood-brain barrier disruption.
As demonstrated within a group of stroke and GBM patients, (123)I-CLINDE SPECT can be used for quantitative assessment of TSPO expression in vivo. Because of the absence of a region devoid of TSPO, reference tissue models should be used with caution. The 2-tissue-compartment kinetic analysis of a 90-min dynamic scan with arterial blood sampling is recommended for the quantification of (123)I-CLINDE binding with SPECT.
本研究首次使用单光子发射计算机断层扫描（SPECT）和 6-氯-2-（4'-（123）I-碘代苯基）-3-（N，N-二乙基）-咪唑并[1,2-a]吡啶-3-乙酰胺（（123）I-CLINDE）对神经患者的转位蛋白（TSPO）结合进行了全面量化。（123）I-CLINDE 与众所周知的 PET 配体（如（18）F-PBR111 和（18）F-DPA-714）在结构上有关。
6 例脑卒中和 4 例多形性胶质母细胞瘤（GBM）患者接受了 150 分钟的动态 SPECT 扫描和动脉采血。其中 4 例患者进行了二次扫描。所有患者均进行了 rs6971 多态性基因分型。在个体 SPECT 扫描和配准的磁共振图像上划定感兴趣区。使用动脉输入或小脑作为参考区的房室和图形模型用于量化（123）I-CLINDE 结合。
在所研究的 6 种模型中，使用动脉输入的 2 组织房室模型对时间活动数据的描述最佳。时间稳定性分析表明，采集时间至少应为 90 分钟。小脑分布容积（VT）的个体间变异性与 TSPO 基因型明显相关。在脑卒中患者中，与对侧小脑相比，梗死周围区的 VT 范围为 1.4 至 3.4，在 GBM 患者中，与小脑相比，肿瘤的 VT 范围为 1.8 至 3.4。在钆外渗区域，（123）I-CLINDE 结合参数没有明显变化。因此，（123）I-CLINDE 结合似乎不会受到血脑屏障破坏的重要影响。
在一组脑卒中患者和 GBM 患者中，（123）I-CLINDE SPECT 可用于体内 TSPO 表达的定量评估。由于没有 TSPO 缺乏的区域，因此应谨慎使用参考组织模型。建议使用动脉采血 90 分钟的动态扫描 2 组织房室动力学分析来定量 SPECT （123）I-CLINDE 结合。
