title: Antiangiogenic tumor treatment: early noninvasive monitoring with USPIO-enhanced MR imaging in mice.
abstract: OBJECTIVE
  To prospectively investigate steady-state blood volume measurements for early quantitative monitoring of antiangiogenic treatment with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging.
  
  
  METHODS
  The institutional animal care committee approved all experiments. HT-1080 fibrosarcoma-bearing nude mice were injected with a thrombogenic vascular targeting agent (VTA) (11 nude mice, 20 tumors) or saline (12 nude mice, 20 tumors). USPIO-enhanced (SH U 555C) MR imaging was performed after the VTA was administered. USPIO-induced changes in tissue R2* (DeltaR2*) were measured with a T2-weighted dual-echo echo-planar imaging sequence, and the vascular volume fraction (VVF) was calculated. Parametric DeltaR2* maps were analyzed with respect to tumor perfusion patterns. Correlative histologic analysis was performed for grading of tissue thrombosis, and tissue perfusion was quantified with fluorescent microbeads. Unpaired Student t test and Spearman nonparametric correlation coefficient were used for statistical analysis.
  
  
  RESULTS
  The DeltaR2* values were significantly (P < .001) reduced shortly after treatment initiation (mean DeltaR2*, 0.017 msec(-1) +/- 0.0014 [standard error] in control animals vs 0.005 msec(-1) +/- 0.0007 in animals that received VTA), which was also reflected by a decrease in the VVF (2.47% +/- 0.18 vs 0.41% +/- 0.48, P < .001). Histologic analysis revealed various degrees of tumor thrombosis after VTA treatment that correlated inversely with the DeltaR2* values (r = -0.83). Moreover, tumor perfusion measurements corroborated the MR results, indicating a significant reduction in tissue perfusion after VTA treatment (mean tissue fluorescence, 570.4 arbitrary units [au] per gram +/- 27 vs 161.7 au/g +/- 17; P < .05).
  
  
  CONCLUSIONS
  USPIO-enhanced MR imaging enables early monitoring of antiangiogenic treatment of tumors.
authors.affiliation: Department of Clinical Radiology, University Hospital Muenster, Albert-Schweitzer-Str 33, D-48129 Muenster, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Persigehl
authors.forename: Ralf
authors.initials: R
authors.lastname: Bieker
authors.forename: Lars
authors.initials: L
authors.lastname: Matuszewski
authors.forename: Alexander
authors.initials: A
authors.lastname: Wall
authors.forename: Torsten
authors.initials: T
authors.lastname: Kessler
authors.forename: Hendrik
authors.initials: H
authors.lastname: Kooijman
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 M
authors.initials: RM
authors.lastname: Mesters
authors.forename: Christoph
authors.initials: C
authors.lastname: Bremer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage*; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide; D005354:Fibrosarcoma / Q000098:blood supply*; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009842:Oligopeptides; D010087:Oxides / Q000008:administration & dosage*; D011446:Prospective Studies; D018709:Statistics, Nonparametric
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D009842:Oligopeptides; D010087:Oxides; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide