title: DW-MRI and (18) F-FLT PET for early assessment of response to radiation therapy associated with hypoxia-driven interventions. Preclinical studies using manipulation of oxygenation and/or dose escalation.
abstract: Early markers of treatment response may help in the management of patients by predicting the outcome of a specific therapeutic intervention. Here, we studied the potential value of diffusion-weighted MRI (DW-MRI) and (18)F-fluorothymidine ((18)F-FLT), markers of cell death and cell proliferation respectively, to predict the response to irradiation. In addition, dose escalation and/or carbogen breathing were used to modulate the response to irradiation. The studies were performed on two hypoxic rat tumor models: rhabdomyosarcoma and 9L-glioma. The rats were imaged using MRI and PET before and two days after the treatment. In both tumor models, changes in ADC (apparent diffusion coefficient) and (18)F-FLT SUV (standardized uptake value) were significantly correlated with the tumor growth delay. For both tumor models, the ADC values increased in all irradiated groups two days after the treatment while they decreased in the untreated groups. At the same time, the uptake of (18)F-FLT increased in the untreated groups and decreased in all treated groups. Yet, ADC values were not sensitive enough to predict the added value of dose escalation or carbogen breathing in either model. Change in (18)F-FLT uptake was able to predict the higher tumor response when using increased dose of irradiation, but not when using a carbogen breathing challenge. Our results also emphasize that the magnitude of change in (18)F-FLT uptake was strongly dependent on the tumor model.
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Ly-Binh-An
authors.initials: LB
authors.lastname: Tran
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Center for Molecular Imaging, Radiotherapy and Oncology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Center for Molecular Imaging, Radiotherapy and Oncology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Oussama
authors.initials: O
authors.lastname: Karroum
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Lionel
authors.initials: L
authors.lastname: Mignion
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Center for Molecular Imaging, Radiotherapy and Oncology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Bol
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Center for Molecular Imaging, Radiotherapy and Oncology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage / Q000737:chemistry; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: MRI; PET; cell death; cell proliferation; hypoxia; irradiation