文章：

利用患者来源的脑膜瘤球体模型探究肽受体放射性核素治疗的放射生物学反应

Investigating the Radiobiological Response to Peptide Receptor Radionuclide Therapy Using Patient-Derived Meningioma Spheroids

原文发布日期：11 July 2024

DOI: 10.3390/cancers16142515

类型: Article

开放获取: 是

英文摘要：

Peptide receptor radionuclide therapy (PRRT) using177Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients. However, current knowledge of the underlying radiation biology is limited, in part due to the lack of appropriate in vitro models. Here, we demonstrate proof-of-concept of a meningioma patient-derived 3D culture model to assess the short-term response to radiation therapies such as PRRT and external beam radiotherapy (EBRT). We established short-term cultures (1 week) for 16 meningiomas with high efficiency and yield. In general, meningioma spheroids retained characteristics of the parental tumor during the initial days of culturing. For a subset of tumors, clear changes towards a more aggressive phenotype were visible over time, indicating that the culture method induced dedifferentiation of meningioma cells. To assess PRRT efficacy, we demonstrated specific uptake of177Lu-DOTA-TATE via somatostatin receptor subtype 2 (SSTR2), which was highly overexpressed in the majority of tumor samples. PRRT induced DNA damage which was detectable for an extended timeframe as compared to EBRT. Interestingly, levels of DNA damage in spheroids after PRRT correlated with SSTR2-expression levels of parental tumors. Our patient-derived meningioma culture model can be used to assess the short-term response to PRRT and EBRT in radiobiological studies. Further improvement of this model should pave the way towards the development of a relevant culture model for assessment of the long-term response to radiation and, potentially, individual patient responses to PRRT and EBRT.

摘要翻译： 

使用¹⁷⁷Lu-DOTA-TATE的肽受体放射性核素治疗（PRRT）近期已被评估用于脑膜瘤患者的治疗。然而，目前对其潜在放射生物学机制的认识仍有限，部分原因在于缺乏合适的体外模型。本研究展示了一种基于脑膜瘤患者来源的三维培养模型的概念验证，用于评估对PRRT及外照射放疗（EBRT）等放射治疗的短期反应。我们高效地建立了16例脑膜瘤的短期培养体系（1周），并获得较高产量。总体而言，脑膜瘤球体在培养初期保留了原始肿瘤的特征。部分肿瘤随时间推移呈现出向更具侵袭性表型转变的明显变化，表明该培养方法诱导了脑膜瘤细胞的去分化。为评估PRRT疗效，我们通过生长抑素受体亚型2（SSTR2）证实了¹⁷⁷Lu-DOTA-TATE的特异性摄取，该受体在大多数肿瘤样本中呈高度过表达。与EBRT相比，PRRT诱导的DNA损伤可在更长时间内被检测到。值得注意的是，PRRT处理后球体的DNA损伤水平与原始肿瘤的SSTR2表达水平呈正相关。本研究所构建的患者来源脑膜瘤培养模型可用于放射生物学研究中对PRRT和EBRT短期反应的评估。该模型的进一步优化将为开发适用于长期放射反应评估的相关培养模型奠定基础，并有望实现针对个体患者对PRRT和EBRT治疗反应的个性化评估。

原文链接：

Investigating the Radiobiological Response to Peptide Receptor Radionuclide Therapy Using Patient-Derived Meningioma Spheroids