title: Prediction of antiangiogenic treatment efficacy by iron oxide enhanced parametric magnetic resonance imaging.
abstract: OBJECTIVE
  Tools for monitoring modern target-specific antiangiogenic and antivascular therapies are highly desirable because treatment strategies are time consuming, expensive, and yet sometimes ineffective. Therefore, the aim of this experimental study was to evaluate the predictive value of steady-state ultrasmall particles of iron oxide (USPIO; SH U 555 C)-enhanced magnetic resonance imaging (MRI) for early assessment of antivascular tumor-treatment effectiveness.
  
  
  METHODS
  Mice were inoculated with an HT-1080 fibrosarcoma xenograft and subjected to target-specific antivascular therapy using a selective thrombogenic vascular-targeting agent (truncated tissue factor fused to RGD peptide) or saline as control. Four to 8 hours after treatment, the USPIO-induced change in the transverse relaxation rate DeltaR2* was measured by MRI, and the vascular volume fraction (VVF) was calculated by calibrating DeltaR2* of the tumor by DeltaR2* of muscle tissue. Treatment response was defined by histologic grading of vascular thrombosis and tumor necrosis.
  
  
  RESULTS
  After thrombogenic treatment, half of the HT-1080 xenograft-bearing animals showed only minor (=nonresponder) whereas the other half showed extensive tumor thrombosis (=responders). For responders, a significant decrease of DeltaR2* and VVF was observed compared with the control group (DeltaR2*: controls: 16 +/- 1 s-1 vs. responder: 4 +/- 2 s-1; P < 0.001) whereas DeltaR2* and VVF remained nearly unchanged for nonresponders (DeltaR2*: nonresponder 14 +/- 2 s-1). VVF and DeltaR2* values correlated inversely with the histologic grading of vascular thrombosis and tumor necrosis (VVF: r = -0.8; DeltaR2*: r = -0.71; P < 0.01).
  
  
  CONCLUSIONS
  USPIO-enhanced MRI allows a noninvasive, early assessment of treatment efficacy of thrombogenic vascular-targeting agents.
authors.affiliation: Department of Clinical Radiology, University of Münster, Münster, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Persigehl
authors.forename: Lars
authors.initials: L
authors.lastname: Matuszewski
authors.forename: Torsten
authors.initials: T
authors.lastname: Kessler
authors.forename: Alexander
authors.initials: A
authors.lastname: Wall
authors.forename: Norbert
authors.initials: N
authors.lastname: Meier
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ebert
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Walter
authors.initials: W
authors.lastname: Heindel
authors.forename: Rolf
authors.initials: R
authors.lastname: Mesters
authors.forename: Christoph
authors.initials: C
authors.lastname: Bremer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage; D005354:Fibrosarcoma / Q000098:blood supply* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000235:genetics; D011237:Predictive Value of Tests; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D013925:Thromboplastin / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D005290:Ferric Compounds; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C526680:tTF-RGD peptide; C000499:ferric oxide; C047981:arginyl-glycyl-aspartic acid; D013925:Thromboplastin