Theranostics 2017; 7(2):436-451. doi:10.7150/thno.17218

Research Paper

Proton MR Spectroscopy and Diffusion MR Imaging Monitoring to Predict Tumor Response to Interstitial Photodynamic Therapy for Glioblastoma

Magali Toussaint1,2, Sophie Pinel1,2, Florent Auger3, Nicolas Durieux3, Magalie Thomassin1,2, Eloise Thomas6, Albert Moussaron6, Dominique Meng1,2, François Plénat1,2, Marine Amouroux1,2, Thierry Bastogne1,2, Céline Frochot4,5, Olivier Tillement6, François Lux6, Muriel Barberi-Heyob1,2✉

1. CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;
2. CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France;
3. Plateforme d'imagerie du vivant - Plateau Préclinique, Université de Lille - Droit et Santé, Lille, France;
4. LRGP UMR 7274 NRS, Nancy, France;
5. LRGP UMR 7274, Université de Lorraine, Nancy, France;
6. ILM UMR 5306 CNRS, Claude Bernard-University, Lyon, France.

Abstract

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.

Keywords: Interstitial photodynamic therapy, Glioblastoma, In Vivo non-invasive imaging, Multifunctional nanoparticles, Image guided therapy, Therapy assessment.

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How to cite this article:
Toussaint M, Pinel S, Auger F, Durieux N, Thomassin M, Thomas E, Moussaron A, Meng D, Plénat F, Amouroux M, Bastogne T, Frochot C, Tillement O, Lux F, Barberi-Heyob M. Proton MR Spectroscopy and Diffusion MR Imaging Monitoring to Predict Tumor Response to Interstitial Photodynamic Therapy for Glioblastoma. Theranostics 2017; 7(2):436-451. doi:10.7150/thno.17218. Available from http://www.thno.org/v07p0436.htm