New intravascular contrast agent applied to dynamic contrast enhanced MR imaging of human breast cancer.

PURPOSE To evaluate the feasibility of using dynamic contrast-enhanced MR imaging with a new intravascular contrast agent in grading human breast cancer. MATERIAL AND METHODS 23 patients with 27 breast tumors (21 carcinomas and 6 fibroadenomas) were examined with dynamic MR imaging after administration of Clariscan, an iron oxide nanoparticle with large T1 relaxivity and a long plasma half life. A 3D T1-weighted gradient echo sequence with an acquisition time of 60 s was repeated at regular intervals of 3-5 min before and up to 1 h after injection of 2 mg/kg b.w. of Clariscan. The endothelial transfer constant, Kps, which reflects overall vascular permeability, and the fractional plasma volume, fPV, were estimated from time-intensity curves acquired from three separate regions of interest (ROIs): whole tumor, a permeability hot spot, and a blood volume hot spot. Kps and fPV were compared to the results of histologic tumor grading (Scarff-Bloom-Richardson, SBR) and microvascular density, MVD. RESULTS A statistically significant correlation between the MR-derived Kps parameters and the SBR score was obtained for the whole tumor ROI (R = 0.70), and for the permeability hot spot ROIs (R = 0.67). A correlation between fPV and SBR was detected for the blood volume hot spot ROIs (R = 0.48). There was no statistically significant correlation between Kps or fPV with MVD. CONCLUSION The results support the hypothesis that dynamic MR with the intravascular contrast agent Clariscan may be used for non-invasive tumor grading.

[1]  A. Bjørnerud,et al.  NC100150 injection, a preparation of optimized iron oxide nanoparticles for positive‐contrast MR angiography , 2000, Journal of magnetic resonance imaging : JMRI.

[2]  D M Shames,et al.  Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media. , 1998, AJR. American journal of roentgenology.

[3]  C. Higgins,et al.  Three‐dimensional MR imaging of pulmonary vessels and parenchyma with NC100150 injection (Clariscan™) , 2000, Journal of magnetic resonance imaging : JMRI.

[4]  C. Kuhl,et al.  MRI of breast tumors , 2000, European Radiology.

[5]  N. Weidner,et al.  Tumor angiogenesis: review of current applications in tumor prognostication. , 1993, Seminars in diagnostic pathology.

[6]  P. Tofts Modeling tracer kinetics in dynamic Gd‐DTPA MR imaging , 1997, Journal of magnetic resonance imaging : JMRI.

[7]  T. Roberts,et al.  Physiologic measurements by contrast‐enhanced MR imaging: Expectations and limitations , 1997, Journal of magnetic resonance imaging : JMRI.

[8]  N. van Bruggen,et al.  Assessing tumor angiogenesis using macromolecular MR imaging contrast media , 1997, Journal of magnetic resonance imaging : JMRI.

[9]  P. Tofts,et al.  Measurement of the blood‐brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts , 1991, Magnetic resonance in medicine.

[10]  B R Rosen,et al.  NMR imaging of changes in vascular morphology due to tumor angiogenesis , 1998, Magnetic resonance in medicine.

[11]  D M Shames,et al.  MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation. , 2001, Radiology.

[12]  D M Shames,et al.  Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: A quantitative noninvasive technique , 1993, Magnetic resonance in medicine.

[13]  H. Dvorak,et al.  Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. , 1989, Biochimica et biophysica acta.

[14]  Rakesh K. Jain,et al.  Transport of molecules across tumor vasculature , 2004, Cancer and Metastasis Reviews.

[15]  H. Dvorak,et al.  Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules. , 1988, The American journal of pathology.

[16]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[17]  J. Boniver,et al.  Assessment of tumor angiogenesis in invasive breast carcinomas: absence of correlation with prognosis and pathological factors , 2000, Virchows Archiv.

[18]  P. Hall,et al.  Prognostic and predictive factors. , 2004, Methods in molecular medicine.

[19]  G. Torheim,et al.  An independent software system for the analysis of dynamic MR images , 1997, Acta radiologica.

[20]  S. Friedman,et al.  Nuclear characteristics as indicators of prognosis in node negative breast cancer patients , 1989, Breast Cancer Research and Treatment.