Steady-state blood volume measurements in experimental tumors with different angiogenic burdens a study in mice.
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.
Bremer
Christoph
C
Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th St, 5406, Charlestown, MA 02129, USA.
Mustafa
Mona
M
Bogdanov
Alex
A
Ntziachristos
Vasilis
V
Petrovsky
Alexander
A
Weissleder
Ralph
R
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
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