title: Early antiangiogenic activity of SU11248 evaluated in vivo by dynamic contrast-enhanced magnetic resonance imaging in an experimental model of colon carcinoma.
abstract: OBJECTIVE
  To compare two dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) techniques in terms of their ability in assessing the early antiangiogenic effect of SU11248, a novel selective multitargeted tyrosine kinase inhibitor, that exhibits direct antitumor and antiangiogenic activity via inhibition of the receptor tyrosine kinases platelet-derived growth factor receptor, vascular endothelial growth factor receptor, KIT, and FLT3.
  
  
  METHODS
  A s.c. tumor model of HT29 human colon carcinoma in athymic mice was used. Two DCE-MRI techniques were used based, respectively, on macromolecular [Gd-diethylenetriaminepentaacetic acid (DTPA)-albumin] and low molecular weight (Gd-DTPA) contrast agents. The first technique provided a quantitative measurement of transendothelial permeability and fractional plasma volume, accepted surrogate markers of tumor angiogenesis. With the second technique, we quantified the initial area under the concentration-time curve, which gives information related to tumor perfusion and vascular permeability. Experiments were done before and 24 hours after a single dose administration of SU11248.
  
  
  RESULTS
  The early antiangiogenic effect of SU11248 was detected by DCE-MRI with macromolecular contrast agent as a 42% decrease in vascular permeability measured in the tumor rim. The effect was also detected by DCE-MRI done with Gd-DTPA as a 31% decrease in the initial area under the concentration-time curve. Histologic slices showed a statistically significant difference in mean vessel density between the treated and control groups.
  
  
  CONCLUSIONS
  The early antiangiogenic activity of SU11248 was detected in vivo by DCE-MRI techniques using either macromolecular or low molecular weight contrast agents. Because DCE-MRI techniques with low molecular weight contrast agents can be used in clinical studies, these results could be relevant for the design of clinical trials based on new paradigms.
authors.affiliation: Dipartimento di Scienze Morfologico-Biomediche, Sezione di Anatomia ed Istologia, Università di Verona, Verona, Italy. pasquina.marzola@univr.it
authors.forename: Pasquina
authors.initials: P
authors.lastname: Marzola
authors.forename: Anna
authors.initials: A
authors.lastname: Degrassi
authors.forename: Laura
authors.initials: L
authors.lastname: Calderan
authors.forename: Paolo
authors.initials: P
authors.lastname: Farace
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolato
authors.forename: Caterina
authors.initials: C
authors.lastname: Crescimanno
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
authors.forename: Anna
authors.initials: A
authors.lastname: Giusti
authors.forename: Enrico
authors.initials: E
authors.lastname: Pesenti
authors.forename: Andrea
authors.initials: A
authors.lastname: Terron
authors.forename: Andrea
authors.initials: A
authors.lastname: Sbarbati
authors.forename: Francesco
authors.initials: F
authors.lastname: Osculati
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003110:Colonic Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy*; D003287:Contrast Media; D019786:Gadolinium DTPA; D019073:HT29 Cells; D006801:Humans; D007089:Image Enhancement; D007211:Indoles / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D011758:Pyrroles / Q000627:therapeutic use*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077210:Sunitinib; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D007211:Indoles; D011758:Pyrroles; D019786:Gadolinium DTPA; D000077210:Sunitinib