title: Magnetic resonance-imaging of the effect of targeted antiangiogenic gene delivery in a melanoma tumour model.
abstract: OBJECTIVE
  We investigated the effect of targeted gene therapy to melanoma tumours (M21) by MR-imaging.
  
  
  METHODS
  M21 and M21-L tumours were grown to a size of 850 mm(3). M21 and M21-L tumours were intravenously treated with an αvβ3-integrin-ligand-coupled nanoparticle (RGDNP)/RAF(-) complex five times every 72 hours. MRI was performed at set time intervals 24h and 72h after the i.v. injection of the complex. The MRI protocol was T1-wt-SE±CM, T2-wt-FSE, DCE-MRI, Diffusion-wt-STEAM-sequence, T2-time obtained on a 1.5-T-GE-MRI device.
  
  
  RESULTS
  The size of the treated M21 tumours kept nearly constant during the treatment phase (847.8±31.4 mm(3) versus 904.8±44.4 mm(3)). The SNR value (T2-weighted images) of the tumours was 36.7±0.6 and dropped down to 30.6±1.9 (p=0.004). At the beginning the SNR value (T1-weighted images) of the tumours after contrast medium application was 42.3±1.9 and dropped down to 28.5±3.0 (p<0.001). In the treatment group the diffusion coefficient increased significantly under therapy (0.54±0.01x10(-3) mm(2)/s versus 0.67±0.04x10(-3) mm(2)/s). The DCE-MRI showed a reduction of the slope and of the Akep of 67.8±4.3 % respectively 64.8±3.3 % compared to baseline.
  
  
  CONCLUSIONS
  Targeted gene delivery therapy induces significant changes in MR-imaging. MRI showed a significant reduction of contrast medium uptake parameters and increase of the diffusion coefficient of the tumours.
  
  
  CONCLUSIONS
  • Treatment with targeted gene-delivery therapy can be monitored by MR imaging • DCE and diffusion-weighted imaging are appropriate methods for monitoring this therapy • Functional changes are significant prior to any morphological changes.
authors.affiliation: Department of Radiology, Lucas MRS Research Center, Stanford School of Medicine, Stanford, CA, USA, hundt@med.uni-marburg.de.
authors.forename: Walter
authors.initials: W
authors.lastname: Hundt
authors.forename: Silke
authors.initials: S
authors.lastname: Steinbach
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
authors.forename: Mykhaylo
authors.initials: M
authors.lastname: Burbelko
authors.forename: Andreas
authors.initials: A
authors.lastname: Kiessling
authors.forename: Jens
authors.initials: J
authors.lastname: Figiel
authors.forename: Samira
authors.initials: S
authors.lastname: Guccione
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003287:Contrast Media / Q000494:pharmacology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D011401:Promoter Regions, Genetic
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media