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Dynamic MRI Enhanced with Albumin–(Gd-DTPA)30 or Ultrasmall Superparamagnetic Iron Oxide Particles (NC100150 Injection) for the Measurement of Microvessel Permeability in Experimental Breast Tumors

2002; Elsevier BV; Volume: 9; Issue: 1 Linguagem: Inglês

10.1016/s1076-6332(03)80413-0

1878-4046

Karl Turetschek, Sabine Huber, Thomas H. Helbich, Eugenia Floyd, Kirk Tarlo, Timothy P. L. Roberts, David M. Shames, Michael F. Wendland, Robert C. Brasch,

Advanced MRI Techniques and Applications

Characteristics of the cell nuclei within human breast tumors, as assayed and scored by the Scarff-Bloom-Richardson (SBR) histopathologic method, correlate with patient prognosis and long-term survival rates ( 1 Le Doussal V Tubiana-Hulin M Friedman S Hacene K Spyratos F Brunet M Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR): an improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. Cancer. 1989; 64: 1914-1921 Crossref PubMed Scopus (356) Google Scholar , 2 Héry M Gioanni J Lalanne CM Namer M Courdi A The DNA labelling index: a prognostic factor in node-negative breast cancer. Breast Cancer Res Treat. 1987; 9: 207-211 Crossref PubMed Scopus (65) Google Scholar ). We have shown previously in rodent mammary tumors that the histopathologic tumor grade correlates with quantitative magnetic resonance imaging (MRI)–derived estimates of tumor microvascular permeability obtained using a prototypic macromolecular contrast medium, albumin–(Gd-DTPA)30 ( 3 Daldrup H Shames DM Wendland M et al. Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media. AJR Am J Roentgenol. 1998; 171: 941-949 Crossref PubMed Scopus (233) Google Scholar ). Microvessel permeability depends on functional and morphologic characteristics of cancer vessels and on physicochemical properties of the injected solute/contrast medium molecule ( 4 Hobbs SK Monsky WL Yuan F et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci U S A. 1998; 95: 4607-4612 Crossref PubMed Scopus (1994) Google Scholar , 5 Dvorak H Nagy J Dvorak J Dvorak A Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules. Am J Pathol. 1988; 133: 95-109 PubMed Google Scholar , 6 Yuan F Dellian M Fukumura D et al. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res. 1995; 55: 3752-3756 PubMed Google Scholar , 7 Jain R Vascular and interstitial barriers to delivery of therapeutic agents in tumors. Cancer Metastasis Rev. 1990; 9: 253-266 Crossref PubMed Scopus (419) Google Scholar ). In this study, we focus on specific characteristics of two contrast media and their influence on MRI-derived estimates of microvessel characteristics. The increased permeability of tumor vessels to macromolecular solutes has been demonstrated repeatedly using albumin–(Gd-DTPA)30, which is used in this study as a reference standard ( 8 Brasch R Pham C Shames D et al. Assessing tumor angiogenesis using macromolecular MR imaging contrast media. J Magn Reson Imaging. 1997; 7: 68-74 Crossref PubMed Scopus (230) Google Scholar , 9 Brasch RC Daldrup H Shames D Wendland M Okuhata Y Rosenau W Macromolecular contrast media-enhanced MRI estimates of microvascular permeability correlate with histopathologic tumor grade. Acad Radiol. 1998; 5: S2-S5 Abstract Full Text PDF PubMed Google Scholar , 10 Schwickert HC Stiskal M Roberts TP et al. Contrast-enhanced MR imaging assessment of tumor capillary permeability: effect of irradiation on delivery of chemotherapy. Radiology. 1996; 198: 893-898 Crossref PubMed Scopus (99) Google Scholar ). Although not previously tested as probes of endothelial hyperpermeability, ultra-small superparamagnetic iron oxide (USPIO) particles, having a mean diameter of approximately 20 nm, were compared in this study to albumin–(Gd-DTPA)30, which is approximately 20% the size of USPIO. Unlike albumin–(Gd-DTPA)30, which is incompletely eliminated and potentially immunogenic, USPIO particles have a favorable pharmacologic and tolerance profile and are now being tested clinically ( 11 Taylor AM Panting JR Keegan J et al. Safety and preliminary findings with the intravascular contrast agent NC100150 injection for MR coronary angiography. J Magn Reson Imaging. 1999; 9: 220-227 Crossref PubMed Scopus (127) Google Scholar ).