title: Tumour biomechanical response to the vascular disrupting agent ZD6126 in vivo assessed by magnetic resonance elastography.
abstract: BACKGROUND
  Magnetic resonance elastography (MRE) is an emerging imaging technique that affords non-invasive quantitative assessment and visualization of tissue mechanical properties in vivo.
  
  
  METHODS
  In this study, MRE was used to quantify (kPa) the absolute value of the complex shear modulus |G*|, elasticity Gd and viscosity Gl of SW620 human colorectal cancer xenografts before and 24 h after treatment with either 200 mg kg(-1) of the vascular disrupting agent ZD6126 (N-acetylcolchinol-O-phosphate) or vehicle control, and the data were compared with changes in water diffusivity measured by diffusion-weighted magnetic resonance imaging.
  
  
  RESULTS
  A heterogeneous distribution of |G*|, Gd and Gl was observed pre-treatment with an intertumoral coefficient of variation of 13% for |G*|. There were no significant changes in the vehicle-treated cohort. In contrast, ZD6126 induced a significant decrease in the tumour-averaged |G*| (P<0.01), Gd (P<0.01) and Gl (P<0.05), and this was associated with histologically confirmed central necrosis. This reduction in tumour viscoelasticity occurred at a time when no significant change in tumour apparent diffusion coefficient (ADC) was observed.
  
  
  CONCLUSIONS
  These data demonstrate that MRE can provide early imaging biomarkers for treatment-induced tumour necrosis.
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Jamin
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK.
authors.forename: J K R
authors.initials: JK
authors.lastname: Boult
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK.
authors.forename: C
authors.initials: C
authors.lastname: Cummings
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Waterton
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ulloa
authors.affiliation: BHF Centre of Excellence, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, UK.
authors.forename: R
authors.initials: R
authors.lastname: Sinkus
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Bamber
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Robinson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001696:Biomechanical Phenomena; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004548:Elasticity; D054459:Elasticity Imaging Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis / Q000139:chemically induced; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D033081:Shear Strength; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; C455219:N-acetylcochinol-O-phosphate; D009943:Organophosphorus Compounds