Su Zhangjie, Roncaroli Federico, Durrenberger Pascal F, Coope David J, Karabatsou Konstantina, Hinz Rainer, Thompson Gerard, Turkheimer Federico E, Janczar Karolina, Du Plessis Daniel, Brodbelt Andrew, Jackson Alan, Gerhard Alexander, Herholz Karl
Wolfson Molecular Imaging Center, University of Manchester, Manchester, United Kingdom.
Division of Brain Science, Imperial College London, London, United Kingdom.
J Nucl Med. 2015 Apr;56(4):512-7. doi: 10.2967/jnumed.114.151621. Epub 2015 Feb 26.
The 18-kDa mitochondrial translocator protein (TSPO) is upregulated in high-grade astrocytomas and can be imaged by PET using the selective radiotracer (11)C-(R)PK11195. We investigated (11)C-(R)PK11195 binding in human gliomas and its relationship with TSPO expression in tumor tissue and glioma-associated microglia/macrophages (GAMs) within the tumors.
Twenty-two glioma patients underwent dynamic (11)C-(R)PK11195 PET scans and perfusion MR imaging acquisition. Parametric maps of (11)C-(R)PK11195 binding potential (BPND) were generated. Coregistered MR/PET images were used to guide tumor biopsy. The tumor tissue was quantitatively assessed for TSPO expression and infiltration of GAMs using immunohistochemistry and double immunofluorescence. The imaging and histopathologic parameters were compared among different histotypes and grades and correlated with each other.
BPND of (11)C-(R)PK11195 in high-grade gliomas was significantly higher than in low-grade astrocytomas and low-grade oligodendrogliomas. TSPO in gliomas was expressed predominantly by neoplastic cells, and its expression correlated positively with BPND in the tumors. GAMs only partially contributed to the overall TSPO expression within the tumors, and TSPO expression in GAMs did not correlate with tumor BPND.
PET with (11)C-(R)PK11195 in human gliomas predominantly reflects TSPO expression in tumor cells. It therefore has the potential to effectively stratify patients who are suitable for TSPO-targeted treatment.
18 kDa的线粒体转位蛋白(TSPO)在高级别星形细胞瘤中上调,并且可以使用选择性放射性示踪剂(11)C-(R)PK11195通过PET进行成像。我们研究了(11)C-(R)PK11195在人类胶质瘤中的结合情况及其与肿瘤组织和肿瘤内胶质瘤相关小胶质细胞/巨噬细胞(GAMs)中TSPO表达的关系。
22例胶质瘤患者接受了动态(11)C-(R)PK11195 PET扫描和灌注磁共振成像采集。生成了(11)C-(R)PK11195结合潜能(BPND)的参数图。使用配准的MR/PET图像指导肿瘤活检。使用免疫组织化学和双重免疫荧光对肿瘤组织的TSPO表达和GAMs浸润进行定量评估。比较不同组织学类型和级别的成像和组织病理学参数,并相互关联。
高级别胶质瘤中(11)C-(R)PK11195的BPND显著高于低级别星形细胞瘤和低级别少突胶质细胞瘤。胶质瘤中的TSPO主要由肿瘤细胞表达,其表达与肿瘤中的BPND呈正相关。GAMs仅部分促成肿瘤内总的TSPO表达,并且GAMs中的TSPO表达与肿瘤BPND不相关。
人类胶质瘤中使用(11)C-(R)PK11195的PET主要反映肿瘤细胞中的TSPO表达。因此,它有潜力有效地对适合TSPO靶向治疗的患者进行分层。