title: Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours.
abstract: OBJECTIVE
  To evaluate effects of a vascular-disrupting agent on rodent tumour models.
  
  
  METHODS
  Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [(18)F]fluorodeoxyglucose micro-positron emission tomography ((18)F-FDG microPET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUV(max)) from FDG microPET were quantified and correlated with postmortem microangiography and histopathology.
  
  
  RESULTS
  In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P < 0.05), corresponding well to histopathology; tumour K decreased from 1 h until 24 h, and partially recovered at 48 h (P < 0.05), parallel to the evolving enhancement ratios (P < 0.05); ADCs varied with tumour viability and perfusion; and SUV(max) dropped at 24 h (P < 0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r = 0.93, P < 0.05).
  
  
  CONCLUSIONS
  The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment.
authors.affiliation: Department of Radiology, University Hospitals, University of Leuven, Leuven, Belgium.
authors.forename: Huaijun
authors.initials: H
authors.lastname: Wang
authors.forename: Junjie
authors.initials: J
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Frederik
authors.initials: F
authors.lastname: De Keyzer
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Feng
authors.forename: Johan
authors.initials: J
authors.lastname: Nuyts
authors.forename: Guy
authors.initials: G
authors.lastname: Marchal
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; C455219:N-acetylcochinol-O-phosphate; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18