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MR Imaging Characterization of Microvessels in Experimental Breast Tumors by Using a Particulate Contrast Agent with Histopathologic Correlation¹

¹ From the Center for Pharmaceutical and Molecular Imaging, Department of Radiology, University of California, San Francisco, Box 0628, 505 Parnassus Ave, San Francisco, CA 94143-0628 (K.T., S.H., T.H., T.P.L.R., D.M.S., M.F.W., R.C.B.); Dept of Radiology, Univ of Vienna, Austria (K.T., T.H.); Dept of Radiology, KH Lainz, Vienna, Austria (S.H.); Dept of Pathology, Pfizer Central Research, Groton, Conn (E.F.); and Nycomed Amersham Imaging, Wayne, Pa (K.S.T.). Received Feb 3, 2000; revision requested Mar 21; final revision received Jun 22; accepted Jun 28. Supported by NIH grant RO1 CA82923-01 and the Cancer Research Fund, State of Calif, interagency agreement #97-12013 with Dept of Health Services, Cancer Research Program. K.T. supported by a grant from the Max Kade Foundation. Address correspondence to R.C.B.

PURPOSE: To define the diagnostic potential of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) particles for the quantitative characterization of tumor microvasculature.

MATERIALS AND METHODS: NC100150 injection, a USPIO in clinical trials, and albumin-(Gd-DTPA)₃₀ were compared at MR imaging on sequential days in the same 19 rats with mammary tumors. Kinetic analysis of dynamic T1-weighted three-dimensional spoiled gradient-recalled imaging data with a two-compartment bidirectional model yielded MR imaging estimates of microvascular permeability (K^PS) and fractional plasma volume (fPV) for each contrast medium.

RESULTS: Strongly positive and significant correlations were observed between MR imaging–derived K^PS estimates and histologic tumor grade with either the soluble albumin-(Gd-DTPA)₃₀ (r = 0.88; P < .001) or larger particulate USPIO (r = 0.82; P < .001). A significant correlation (P < .05) was observed with each contrast medium between K^PS and the histologic microvascular density (MVD), an angiogenesis indicator. Despite the considerable difference in molecule and particle sizes, no significant difference was observed in the MR imaging–derived mean permeability values generated with the two contrast media.

CONCLUSION: USPIO, a macromolecular particulate MR imaging contrast agent, can be applied successfully to characterize tumor microvessels in animals. USPIO-derived K^PS correlated strongly with histopathologic tumor grade, MVD, and K^PS values derived by using albumin-(Gd-DTPA)₃₀ in the same tumors.

Index terms: Animals • Breast neoplasms, 00.30 • Contrast media • Iron • Magnetic resonance (MR), three-dimensional, 00.121411, 00.121412, 00.121419

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