高级别胶质瘤中的生长抑素受体2型：使用（68）Ga-DOTA肽的PET/CT、与预后标志物的相关性以及对靶向放疗的意义
Somatostatin receptor subtype 2 in high-grade gliomas: PET/CT with (68)Ga-DOTA-peptides, correlation to prognostic markers, and implications for targeted radiotherapy.
作者信息
Kiviniemi Aida, Gardberg Maria, Frantzén Janek, Pesola Marko, Vuorinen Ville, Parkkola Riitta, Tolvanen Tuula, Suilamo Sami, Johansson Jarkko, Luoto Pauliina, Kemppainen Jukka, Roivainen Anne, Minn Heikki
机构信息
Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521 Turku, Finland ; Department of Radiology, Medical Imaging Centre of Southwest Finland, Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
Department of Pathology, Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
出版信息
EJNMMI Res. 2015 Apr 22;5:25. doi: 10.1186/s13550-015-0106-2. eCollection 2015.
BACKGROUND
High-grade gliomas (HGGs) express somatostatin receptors (SSTR), rendering them candidates for peptide receptor radionuclide therapy (PRRT). Our purpose was to evaluate the potential of (68)Ga-DOTA-1-Nal(3)-octreotide ((68)Ga-DOTANOC) or (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTATOC) to target SSTR subtype 2 (SSTR2) in HGGs, and to study the association between SSTR2 expression and established biomarkers.
METHODS
Twenty-seven patients (mean age 52 years) with primary or recurrent HGG prospectively underwent (68)Ga-DOTA-peptide positron emission tomography/computed tomography (PET/CT) before resection. Maximum standardized uptake values (SUVmax) and receptor binding potential (BP) were calculated on PET/CT and disruption of blood-brain barrier (BBB) from contrast-enhanced T1-weighted magnetic resonance imaging (MRI-T1-Gad). Tumor volume concordance between PET and MRI-T1-Gad was assessed by Dice similarity coefficient (DC) and correlation by Spearman's rank. Immunohistochemically determined SSTR2 status was compared to receptor imaging findings, prognostic biomarkers, and survival with Kruskal-Wallis, Pearson chi-square, and multivariate Cox regression, respectively.
RESULTS
All 19 HGGs with disrupted BBB demonstrated tracer uptake. Tumor SUVmax (2.25 ± 1.33) correlated with MRI-T1-Gad (r = 0.713, P = 0.001) although DC 0.41 ± 0.19 suggested limited concordance. SSTR2 immunohistochemistry was regarded as positive in nine HGGs (32%) but no correlation with SUVmax or BP was found. By contrast, SSTR2 expression was associated with IDH1 mutation (P = 0.007), oligodendroglioma component (P = 0.010), lower grade (P = 0.005), absence of EGFR amplification (P = 0.021), and longer progression-free survival (HR 0.161, CI 0.037 to 0.704, P = 0.015).
CONCLUSIONS
In HGGs, uptake of (68)Ga-DOTA-peptides is associated with disrupted BBB and cannot be predicted by SSTR2 immunohistochemistry. Thus, PET/CT shows limited value to detect HGGs suitable for PRRT. However, high SSTR2 expression portends favorable outcome along with established biomarkers such as IDH1 mutation.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01460706.
背景
高级别胶质瘤（HGG）表达生长抑素受体（SSTR），使其成为肽受体放射性核素治疗（PRRT）的候选对象。我们的目的是评估（68）Ga-DOTA-1-Nal（3）-奥曲肽（（68）Ga-DOTANOC）或（68）Ga-DOTA-Tyr（3）-奥曲肽（（68）Ga-DOTATOC）靶向HGG中SSTR2亚型的潜力，并研究SSTR2表达与既定生物标志物之间的关联。
方法
27例原发性或复发性HGG患者（平均年龄52岁）在切除术前前瞻性地接受了（68）Ga-DOTA肽正电子发射断层扫描/计算机断层扫描（PET/CT）。在PET/CT上计算最大标准化摄取值（SUVmax）和受体结合潜能（BP），并通过对比增强T1加权磁共振成像（MRI-T1-Gad）评估血脑屏障（BBB）的破坏情况。通过Dice相似系数（DC）评估PET与MRI-T1-Gad之间的肿瘤体积一致性，并通过Spearman秩相关分析进行相关性分析。分别采用Kruskal-Wallis检验、Pearson卡方检验和多变量Cox回归分析比较免疫组化确定的SSTR2状态与受体显像结果、预后生物标志物及生存率。
结果
所有19例BBB破坏的HGG均显示示踪剂摄取。肿瘤SUVmax（2.25±1.33）与MRI-T1-Gad相关（r = 0.713，P = 0.001），尽管DC为0.41±0.19表明一致性有限。9例HGG（32%）的SSTR2免疫组化被视为阳性，但未发现与SUVmax或BP相关。相比之下，SSTR2表达与IDH1突变（P = 0.007）、少突胶质细胞瘤成分（P = 0.010）、低级别（P = 0.005）、EGFR扩增缺失（P = 0.021）以及更长的无进展生存期相关（HR 0.161，CI 0.037至0.704，P = 0.015）。
结论
在HGG中，（68）Ga-DOTA肽的摄取与BBB破坏相关，且不能通过SSTR2免疫组化预测。因此，PET/CT在检测适合PRRT的HGG方面价值有限。然而，高SSTR2表达与IDH1突变等既定生物标志物一样预示着良好的预后。
试验注册
ClinicalTrials.gov NCT01460706。
Zotero 插件