BioMaps, Service Hospitalier Frédéric Joliot, CEA, CNRS, Inserm, University of Paris-Saclay, 4 Place du Général Leclerc, 91401 Orsay, France.
Institut de Recerca, Sant Joan de Déu Hospital, Carrer de Sant Quinti, 77, 08041 Barcelona, Spain.
Int J Mol Sci. 2022 Oct 18;23(20):12476. doi: 10.3390/ijms232012476.
Diffuse intrinsic pontine gliomas (DIPG), the first cause of cerebral pediatric cancer death, will greatly benefit from specific and non-invasive biomarkers for patient follow-up and monitoring of drug efficacy. Since biopsies are challenging for brain tumors, molecular imaging may be a technique of choice to target and follow tumor evolution. So far, MR remains the imaging technique of reference for DIPG, although it often fails to define the extent of tumors, an essential parameter for therapeutic efficacy assessment. Thanks to its high sensitivity, positron emission tomography (PET) offers a unique way to target specific biomarkers in vivo. We demonstrated in a patient-derived orthotopic xenograft (PDOX) model in the rat that the translocator protein of 18 kDa (TSPO) may be a promising biomarker for monitoring DIPG tumors. We studied the distribution of 18F-DPA-714, a TSPO radioligand, in rats inoculated with HSJD-DIPG-007 cells. The primary DIPG human cell line HSJD-DIPG-007 highly represents this pediatric tumor, displaying the most prevalent DIPG mutations, H3F3A (K27M) and ACVR1 (R206H). Kinetic modeling and parametric imaging using the brain 18F-DPA-714 PET data enabled specific delineation of the DIPG tumor area, which is crucial for radiotherapy dose management.
弥漫性内在脑桥神经胶质瘤（DIPG）是小儿脑癌死亡的首要原因，如果能找到针对该疾病的特异性、非侵入性生物标志物，用于患者随访和药物疗效监测，将大为受益。由于对脑肿瘤进行活检具有挑战性，因此分子成像可能是一种靶向和跟踪肿瘤演变的首选技术。到目前为止，磁共振成像（MR）仍然是 DIPG 的参考成像技术，尽管它往往无法确定肿瘤的范围，而这是评估治疗效果的一个重要参数。正电子发射断层扫描（PET）凭借其高灵敏度，为靶向特定生物标志物提供了一种独特的体内方法。我们在大鼠的 DIPG 患者来源的原位异种移植（PDOX）模型中证明，18kDa 转位蛋白（TSPO）可能是监测 DIPG 肿瘤的一种很有前途的生物标志物。我们研究了 18F-DPA-714（一种 TSPO 放射性配体）在 HSJD-DIPG-007 细胞接种大鼠中的分布情况。原发性 DIPG 人细胞系 HSJD-DIPG-007 高度代表了这种小儿肿瘤，显示出最常见的 DIPG 突变，H3F3A（K27M）和 ACVR1（R206H）。使用大脑 18F-DPA-714 PET 数据进行的动力学建模和参数成像，能够特异性地划定 DIPG 肿瘤区域，这对放疗剂量管理至关重要。
