title: Increase in tumour permeability following TGF-beta type I receptor-inhibitor treatment observed by dynamic contrast-enhanced MRI.
abstract: BACKGROUND
  To enhance the success rate of nanocarrier-mediated chemotherapy combined with an anti-angiogenic agent, it is crucial to identify parameters for tumour vasculature that can predict a response to the treatment of the anti-angiogenic agent.
  
  
  METHODS
  To apply transforming growth factor (TGF)-beta type I receptor (TbetaR-I) inhibitor, A-83-01, to combined therapy, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was carried out in mice bearing colon 26 cells using gadolinium (Gd)-DTPA and for its liposomal formulation to evaluate changes in tumour microvasculature following A-83-01. Tumour vascular parameters from DCE-MRI were compared with histological assessment and apparent diffusion coefficient of water in tumour generated by diffusion-weighted MRI.
  
  
  RESULTS
  Contrary to evaluations reported for anti-angiogenic agents, A-83-01 treatment increased the initial area under the Gd concentration-time curve (IAUGC60), volume transfer constant (K(trans)) and fractional plasma volume (v(p)) significantly within 24 h, that was positively related to alpha-smooth muscle actin-positive pericyte coverage and tumour cell proliferation, and was correlated inversely with the apparent diffusion coefficient. The vascular function of the tumour improved by A-83-01 treatment was well assessed on post-liposomal Gd-DTPA-enhanced MR images, which predicted delivery of a liposomal drug to the tumour.
  
  
  CONCLUSIONS
  These findings suggest that DCE-MRI and, in particular, K(trans) and v(p) quantitation, provide important additional information about tumour vasculature by A-83-01 treatment.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Minowa
authors.forename: K
authors.initials: K
authors.lastname: Kawano
authors.forename: H
authors.initials: H
authors.lastname: Kuribayashi
authors.forename: K
authors.initials: K
authors.lastname: Shiraishi
authors.forename: T
authors.initials: T
authors.lastname: Sugino
authors.forename: Y
authors.initials: Y
authors.lastname: Hattori
authors.forename: M
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Y
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003287:Contrast Media; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000494:pharmacology*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D013859:Thiocarbamates / Q000494:pharmacology*; D013882:Thiosemicarbazones
chemical_list: C507011:A-83-01; D003287:Contrast Media; D011720:Pyrazoles; D018125:Receptors, Transforming Growth Factor beta; D013859:Thiocarbamates; D013882:Thiosemicarbazones; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D019786:Gadolinium DTPA