Wolfson Molecular Imaging Centre, University of Manchester, 27 Palatine Road, Manchester, UK.
Eur J Nucl Med Mol Imaging. 2013 Sep;40(9):1406-19. doi: 10.1007/s00259-013-2447-2. Epub 2013 May 29.
Translocator protein (TSPO) is a biomarker of neuroinflammation that can be imaged by PET using [¹¹C]-(R)PK11195. We sought to characterize the [¹¹C]-(R)PK11195 kinetics in gliomas of different histotypes and grades, and to compare two reference tissue input functions (supervised cluster analysis versus cerebellar grey matter) for the estimation of [¹¹C]-(R)PK11195 binding in gliomas and surrounding brain structures.
Twenty-three glioma patients and ten age-matched controls underwent structural MRI and dynamic [¹¹C]-(R)PK11195 PET scans. Tissue time-activity curves (TACs) were extracted from tumour regions as well as grey matter (GM) and white matter (WM) of the brains. Parametric maps of binding potential (BPND) were generated with the simplified reference tissue model using the two input functions, and were compared with each other. TSPO expression was assessed in tumour tissue sections by immunohistochemistry.
Three types of regional kinetics were observed in individual tumour TACs: GM-like kinetics (n=6, clearance of the tracer similar to that in cerebellar GM), WM-like kinetics (n=8, clearance of the tracer similar to that in cerebral WM) and a form of mixed kinetics (n=9, intermediate rate of clearance). Such kinetic patterns differed between low-grade astrocytomas (WM-like kinetics) and oligodendrogliomas (GM-like and mixed kinetics), but were independent of tumour grade. There was good agreement between parametric maps of BPND derived from the two input functions in all controls and 10 of 23 glioma patients. In 13 of the 23 patients, BPND values derived from the supervised cluster input were systematically smaller than those using the cerebellar input. Immunohistochemistry confirmed that TSPO expression increased with tumour grade.
The three types of [¹¹C]-(R)PK11195 kinetics in gliomas are determined in part by tracer delivery, and indicated that kinetic analysis is a valuable tool in the study of gliomas with the potential for in vivo discrimination between low-grade astrocytomas and oligodendrogliomas. Supervised cluster and cerebellar input functions produced consistent BPND estimates in approximately half of the gliomas investigated, but had a systematic difference in the remainder. The cerebellar input is preferred based on theoretical and practical considerations.
转位蛋白（TSPO）是神经炎症的生物标志物，可通过 PET 使用 [¹¹C] - （R）PK11195 进行成像。我们试图描述不同组织类型和分级的胶质瘤中 [¹¹C] - （R）PK11195 的动力学，并比较两种参考组织输入函数（监督聚类分析与小脑灰质），以估计胶质瘤和周围脑结构中 [¹¹C] - （R）PK11195 的结合。
23 名胶质瘤患者和 10 名年龄匹配的对照者接受结构 MRI 和动态 [¹¹C] - （R）PK11195 PET 扫描。从肿瘤区域以及大脑的灰质（GM）和白质（WM）中提取组织时间活性曲线（TAC）。使用简化参考组织模型，通过两种输入函数生成结合潜能（BPND）的参数图，并相互比较。通过免疫组织化学评估肿瘤组织切片中的 TSPO 表达。
在单个肿瘤 TAC 中观察到三种类型的区域动力学：GM 样动力学（n=6，示踪剂清除与小脑 GM 相似），WM 样动力学（n=8，示踪剂清除与大脑 WM 相似）和混合动力学形式（n=9，清除速度中等）。在低级别星形细胞瘤（WM 样动力学）和少突胶质细胞瘤（GM 样和混合动力学）中，这种动力学模式不同，但与肿瘤分级无关。在所有对照者和 23 名胶质瘤患者中的 10 名中，来自两种输入函数的 BPND 参数图之间存在良好的一致性。在 23 名患者中的 13 名中，来自监督聚类输入的 BPND 值系统地小于使用小脑输入的 BPND 值。免疫组织化学证实 TSPO 表达随肿瘤分级而增加。
胶质瘤中 [¹¹C] - （R）PK11195 的三种动力学类型部分由示踪剂输送决定，并表明动力学分析是研究胶质瘤的有价值工具，具有在体内区分低级别星形细胞瘤和少突胶质细胞瘤的潜力。在大约一半的研究胶质瘤中，监督聚类和小脑输入函数产生了一致的 BPND 估计值，但在其余的胶质瘤中存在系统差异。基于理论和实践考虑，更倾向于小脑输入。
