title: Proton MR Spectroscopy and Diffusion MR Imaging Monitoring to Predict Tumor Response to Interstitial Photodynamic Therapy for Glioblastoma.
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.
authors.affiliation: CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Toussaint
authors.affiliation: CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Pinel
authors.affiliation: Plateforme d'imagerie du vivant - Plateau Préclinique, Université de Lille - Droit et Santé, Lille, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Auger
authors.affiliation: Plateforme d'imagerie du vivant - Plateau Préclinique, Université de Lille - Droit et Santé, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Durieux
authors.affiliation: CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Thomassin
authors.affiliation: ILM UMR 5306 CNRS, Claude Bernard-University, Lyon, France.
authors.forename: Eloise
authors.initials: E
authors.lastname: Thomas
authors.affiliation: ILM UMR 5306 CNRS, Claude Bernard-University, Lyon, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Moussaron
authors.affiliation: CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Meng
authors.affiliation: CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: François
authors.initials: F
authors.lastname: Plénat
authors.affiliation: CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Amouroux
authors.affiliation: CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bastogne
authors.affiliation: LRGP UMR 7274 NRS, Nancy, France;; LRGP UMR 7274, Université de Lorraine, Nancy, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Frochot
authors.affiliation: ILM UMR 5306 CNRS, Claude Bernard-University, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: ILM UMR 5306 CNRS, Claude Bernard-University, Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.affiliation: CRAN UMR 7039, CNRS, Vandœuvre-lès-Nancy, France;; CRAN UMR 7039, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Barberi-Heyob
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage; D004195:Disease Models, Animal; D016903:Drug Monitoring / Q000379:methods*; D005909:Glioblastoma / Q000175:diagnosis* / Q000628:therapy*; D064593:Heterografts; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011522:Protons; D011923:Rats, Nude; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D017319:Photosensitizing Agents; D011522:Protons
keywords: Glioblastoma; Image guided therapy; In Vivo non-invasive imaging; Interstitial photodynamic therapy; Multifunctional nanoparticles; Therapy assessment.