title: Steady-state blood volume measurements in experimental tumors with different angiogenic burdens a study in mice.
abstract: OBJECTIVE
  To experimentally validate the effectiveness of magnetic resonance (MR) imaging enhanced with long-circulating iron oxide for measurement of vascular volume fractions (VVFs) as indicators of angiogenesis in different experimental tumor models.
  
  
  METHODS
  Tumors with differing degrees of angiogenesis-9L rodent gliosarcoma, DU4475 human mammary adenocarcinoma, HT1080 human fibrosarcoma, and EOMA hemangioendothelioma--were implanted in nude mice. Tumoral VVFs were measured at submillimeter voxel resolutions by using 1.5-T MR imaging. A technetium-labeled intravascular radiotracer was injected into a subset of the animals to validate the MR imaging measurements. Microvessel density and vascular endothelial growth factor (VEGF) also were measured. Statistical analysis was performed with analysis of variance.
  
  
  RESULTS
  High-resolution multisection MR maps of tumor blood volume were obtained in all tumor models. Mean tumoral VVF differed significantly among the different tumors: 2.1% +/- 0.3 (standard error of mean) for 9L gliosarcoma, 3.1% +/- 0.4 for DU4475 mammary adenocarcinoma, 5.5% +/- 0.8 for HT1080 fibrosarcoma, and 6.6% +/- 0.9 for EOMA hemangioendothelioma (P <.01). There was a strong correlation between the MR imaging and radiotracer measurements. There was considerable intra- and intertumoral heterogeneity among the VVFs. MR imaging measurements were in accordance with conventional measurements of angiogenesis, such as microvessel density count and VEGF.
  
  
  CONCLUSIONS
  Measurements of tumoral VVF at high-resolution MR imaging with long-circulating iron oxide are feasible and correlate with angiogenic burden in experimental tumor models.
authors.affiliation: Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th St, 5406, Charlestown, MA 02129, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bremer
authors.forename: Mona
authors.initials: M
authors.lastname: Mustafa
authors.forename: Alex
authors.initials: A
authors.lastname: Bogdanov
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.forename: Alexander
authors.initials: A
authors.lastname: Petrovsky
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology; D000818:Animals; D001811:Blood Volume Determination / Q000379:methods*; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000032:analysis; D005290:Ferric Compounds / Q000097:blood; D005354:Fibrosarcoma / Q000503:physiopathology; D018316:Gliosarcoma / Q000503:physiopathology; D006390:Hemangioendothelioma / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D008325:Mammary Neoplasms, Experimental / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation / Q000033:anatomy & histology; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D005290:Ferric Compounds; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C000499:ferric oxide