title: Assessment of multiparametric MRI in a human glioma model to monitor cytotoxic and anti-angiogenic drug effects.
abstract: Early imaging or blood biomarkers of tumor response is needed to customize anti-tumor therapy on an individual basis. This study evaluates the sensitivity and relevance of five potential MRI biomarkers. Sixty nude rats were implanted with human glioma cells (U-87 MG) and randomized into three groups: one group received an anti-angiogenic treatment (Sorafenib), a second a cytotoxic drug [1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU (Carmustine)] and a third no treatment. The tumor volume, apparent diffusion coefficient (ADC) of water, blood volume fraction (BVf), microvessel diameter (vessel size index, VSI) and vessel wall integrity (contrast enhancement, CE) were monitored before and during treatment. Sorafenib reduced tumor CE as early as 1 day after treatment onset. By 4 days after treatment onset, tumor BVf was reduced and tumor VSI was increased. By 14 days after treatment onset, ADC was increased and the tumor growth rate was reduced. With BCNU, ADC was increased and the tumor growth rate was reduced 14 days after treatment onset. Thus, the estimated MRI parameters were sensitive to treatment at different times after treatment onset and in a treatment-dependent manner. This study suggests that multiparametric MR monitoring could allow the assessment of new anti-tumor drugs and the optimization of combined therapies.
authors.affiliation: Oncodesign Biotechnology, Dijon, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lemasson
authors.forename: Thomas
authors.initials: T
authors.lastname: Christen
authors.forename: Xavier
authors.initials: X
authors.lastname: Tizon
authors.forename: Régine
authors.initials: R
authors.lastname: Farion
authors.forename: Nadège
authors.initials: N
authors.lastname: Fondraz
authors.forename: Peggy
authors.initials: P
authors.lastname: Provent
authors.forename: Christoph
authors.initials: C
authors.lastname: Segebarth
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Barbier
authors.forename: Philippe
authors.initials: P
authors.lastname: Genne
authors.forename: Olivier
authors.initials: O
authors.lastname: Duchamp
authors.forename: Chantal
authors.initials: C
authors.lastname: Remy
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use; D001810:Blood Volume / Q000187:drug effects; D002330:Carmustine / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D008954:Models, Biological; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011923:Rats, Nude; D000077157:Sorafenib; D013194:Staining and Labeling; D016019:Survival Analysis
chemical_list: D020533:Angiogenesis Inhibitors; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D002330:Carmustine