Toussaint Magali, Pinel Sophie, Auger Florent, Durieux Nicolas, Thomassin Magalie, Thomas Eloise, Moussaron Albert, Meng Dominique, Plénat François, Amouroux Marine, Bastogne Thierry, Frochot Céline, Tillement Olivier, Lux François, Barberi-Heyob Muriel
CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
Plateforme d'imagerie du vivant - Plateau Préclinique, Université de Lille - Droit et Santé, Lille, France.
Theranostics. 2017 Jan 5;7(2):436-451. doi: 10.7150/thno.17218. eCollection 2017.
Despite recent progress in conventional therapeutic approaches, the vast majority of glioblastoma recur locally, indicating that a more aggressive local therapy is required. Interstitial photodynamic therapy (iPDT) appears as a very promising and complementary approach to conventional therapies. However, an optimal fractionation scheme for iPDT remains the indispensable requirement. To achieve that major goal, we suggested following iPDT tumor response by a non-invasive imaging monitoring. Nude rats bearing intracranial glioblastoma U87MG xenografts were treated by iPDT, just after intravenous injection of AGuIX® nanoparticles, encapsulating PDT and imaging agents. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) allowed us an original longitudinal follow-up of post-treatment effects to discriminate early predictive markers. We successfully used conventional MRI, T2 star (T2*), Diffusion Weighted Imaging (DWI) and MRS to extract relevant profiles on tissue cytoarchitectural alterations, local vascular disruption and metabolic information on brain tumor biology, achieving earlier assessment of tumor response. From one day post-iPDT, DWI and MRS allowed us to identify promising markers such as the Apparent Diffusion Coefficient (ADC) values, lipids, choline and myoInositol levels that led us to distinguish iPDT responders from non-responders. All these responses give us warning signs well before the tumor escapes and that the growth would be appreciated.
尽管传统治疗方法最近取得了进展，但绝大多数胶质母细胞瘤仍会局部复发，这表明需要更积极的局部治疗。间质光动力疗法（iPDT）似乎是一种非常有前景的传统治疗补充方法。然而，iPDT的最佳分割方案仍然是必不可少的要求。为了实现这一主要目标，我们建议通过无创成像监测来跟踪iPDT的肿瘤反应。在静脉注射包裹了光动力疗法和成像剂的AGuIX®纳米颗粒后，对携带颅内胶质母细胞瘤U87MG异种移植瘤的裸鼠进行iPDT治疗。磁共振成像（MRI）和磁共振波谱（MRS）使我们能够对治疗后的效果进行原始的纵向跟踪，以区分早期预测标志物。我们成功地使用传统MRI、T2星（T2*）、扩散加权成像（DWI）和MRS来提取有关组织细胞结构改变、局部血管破坏以及脑肿瘤生物学代谢信息的相关特征，从而实现对肿瘤反应的早期评估。在iPDT治疗后的一天，DWI和MRS使我们能够识别出有前景的标志物，如表观扩散系数（ADC）值、脂质、胆碱和肌醇水平，这些标志物使我们能够区分iPDT反应者和无反应者。所有这些反应在肿瘤逃逸和生长可被察觉之前就给了我们警示信号。
