title: Multimodal imaging of tumor response to sorafenib combined with radiation therapy: comparison between diffusion-weighted MRI, choline spectroscopy and 18F-FLT PET imaging.
abstract: The purpose of this study was to determine the value of different imaging modalities, that is, magnetic resonance imaging/spectroscopy (MRI/MRS) and positron emission tomography (PET), to assess early tumor response to sorafenib with or without radiotherapy. Diffusion-weighted (DW)-MRI, choline (1)H MRS at 11.7 T, and (18)F-FLT PET imaging were used to image fibrosarcoma (FSaII) tumor-bearing mice over time. The imaging markers were compared with apoptosis cell death and cell proliferation measurements assessed by histology. Anti-proliferative effects of sorafenib were evidenced by (1)H MRS and (18)F-FLT PET after 2 days of treatment with sorafenib, with no additional effect of the combination with radiation therapy, results that are in agreement with Ki67 staining. Apparent diffusion coefficient calculated using DW-MRI was not modified after 2 days of treatment with sorafenib, but showed significant increase 24 h after 2 days of sorafenib treatment combined with consecutive irradiation. The three imaging markers were able to show early tumor response as soon as 24 h after treatment initiation, with choline MRS and (18)F-FLT being sensitive to sorafenib in monotherapy as well as in combined therapy with irradiation, whereas DW-MRI was only sensitive to the combination of sorafenib with radiotherapy.
authors.affiliation: Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Université Catholique de Louvain, Belgium, Avenue Mounier 73, B-1200 Brussels, Belgium.
authors.forename: Oussama
authors.initials: O
authors.lastname: Karroum
authors.forename: Lionel
authors.initials: L
authors.lastname: Mignion
authors.forename: Julie
authors.initials: J
authors.lastname: Kengen
authors.forename: Linda
authors.initials: L
authors.lastname: Karmani
authors.forename: Philippe
authors.initials: P
authors.lastname: Levêque
authors.forename: Pierre
authors.initials: P
authors.lastname: Danhier
authors.forename: Julie
authors.initials: J
authors.lastname: Magat
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D002794:Choline / Q000032:analysis*; D015224:Dideoxynucleosides; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005354:Fibrosarcoma / Q000175:diagnosis* / Q000628:therapy*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D020266:Radiotherapy, Conformal / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077157:Sorafenib; D013382:Subtraction Technique; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015224:Dideoxynucleosides; D010671:Phenylurea Compounds; D019275:Radiopharmaceuticals; D009536:Niacinamide; D000077157:Sorafenib; D002794:Choline; C002854:alovudine