Bashir Asma, Vestergaard Mark Bitsch, Binderup Tina, Broholm Helle, Marner Lisbeth, Ziebell Morten, Fugleholm Kåre, Mathiesen Tiit, Kjær Andreas, Law Ian
Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Eur J Nucl Med Mol Imaging. 2020 Oct;47(11):2577-2588. doi: 10.1007/s00259-020-04759-1. Epub 2020 Mar 13.
DOTA-D-Phe-Tyr-octreotide with gallium-68 ([Ga]Ga-DOTA-TOC) is one of the PET tracers that forms the basis for peptide receptor radionuclide therapy based on somatostatin receptor subtype 2 (SSTR2) expression in meningiomas. Yet, the quantitative relationship between [Ga]Ga-DOTA-TOC accumulation and SSTR2 is unknown. We conducted a correlative analysis of a range of [Ga]Ga-DOTA-TOC PET metric(s) as imaging surrogate(s) of the receptor binding in meningiomas by correlating the PET results with SSTR2 expression from surgical specimens. We additionally investigated possible influences of secondary biological factors such as vascularization, inflammation and proliferation.
Fifteen patients with MRI-presumed or recurrent meningiomas underwent a 60-min dynamic [Ga]Ga-DOTA-TOC PET/CT before surgery. The PET data comprised maximum and mean standardized uptake values (SUV, SUV) with and without normalization to reference regions, and quantitative measurements derived from kinetic modelling using a reversible two-tissue compartment model with the fractional blood volume (V). Expressions of SSTR2 and proliferation (Ki-67, phosphohistone-H3, proliferating cell nuclear antigen) were determined by immunohistochemistry and/or quantitative polymerase chain reaction (qPCR), while biomarkers of vascularization (vascular endothelial growth factor A (VEGFA), endothelial marker CD34) and inflammation (cytokine interleukin-18, microglia/macrophage-specific marker CD68) by qPCR.
Histopathology revealed 12 World Health Organization (WHO) grade I and three WHO grade II meningiomas showing no link to SSTR2. The majority of [Ga]Ga-DOTA-TOC PET metrics showed significant associations with SSTR2 protein, while all PET metrics were positively correlated with SSTR2 mRNA with the best results for mean tumour-to-blood ratio (TBR) (r = 0.757, P = 0.001) and SUV (r = 0.714, P = 0.003). Significant positive correlations were also found between [Ga]Ga-DOTA-TOC PET metrics, and VEGFA and V. SSTR2 mRNA was moderately correlated with VEGFA (r = 0.539, P = 0.038). Neither [Ga]Ga-DOTA-TOC PET metrics nor SSTR2 were correlated with proliferation or inflammation.
[Ga]Ga-DOTA-TOC accumulation in meningiomas is associated with SSTR2 binding and vascularization with TBR being the best PET metric for assessing SSTR2.
镓-68标记的DOTA-D-苯丙氨酸-酪氨酸-奥曲肽（[Ga]Ga-DOTA-TOC）是一种正电子发射断层显像（PET）示踪剂，是基于脑膜瘤中生长抑素受体2型（SSTR2）表达的肽受体放射性核素治疗的基础之一。然而，[Ga]Ga-DOTA-TOC摄取与SSTR2之间的定量关系尚不清楚。我们通过将PET结果与手术标本中的SSTR2表达进行关联分析，对一系列[Ga]Ga-DOTA-TOC PET指标作为脑膜瘤受体结合的成像替代指标进行了相关性分析。我们还研究了血管生成、炎症和增殖等二级生物学因素的可能影响。
15例MRI诊断为脑膜瘤或复发性脑膜瘤的患者在手术前行60分钟动态[Ga]Ga-DOTA-TOC PET/CT检查。PET数据包括标准化摄取值（SUV）的最大值和平均值，有或无参考区域归一化，以及使用具有分数血容量（V）的可逆双组织室模型从动力学建模得出的定量测量值。通过免疫组织化学和/或定量聚合酶链反应（qPCR）测定SSTR2和增殖（Ki-67、磷酸化组蛋白-H3、增殖细胞核抗原）的表达，而通过qPCR测定血管生成（血管内皮生长因子A（VEGFA）、内皮标志物CD34）和炎症（细胞因子白细胞介素-18、小胶质细胞/巨噬细胞特异性标志物CD68）的生物标志物。
组织病理学显示12例世界卫生组织（WHO）I级和3例WHO II级脑膜瘤，与SSTR2无关联。大多数[Ga]Ga-DOTA-TOC PET指标与SSTR蛋白有显著相关性，而所有PET指标与SSTR2 mRNA呈正相关，平均肿瘤与血液比值（TBR）结果最佳（r = 0.757，P = 0.001）和SUV（r = 0.714，P = 0.003）。[Ga]Ga-DOTA-TOC PET指标与VEGFA和V之间也发现显著正相关。SSTR2 mRNA与VEGFA中度相关（r = 0.539，P = 0.038）。[Ga]Ga-DOTA-TOC PET指标和SSTR2均与增殖或炎症无关。
脑膜瘤中[Ga]Ga-DOTA-TOC的摄取与SSTR2结合和血管生成相关，TBR是评估SSTR2的最佳PET指标。
