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Experimental Studies |
1 From the Departments of Clinical Radiology (T.P., L.M., A.W., N.M., W.H., C.B.) and Medicine/Hematology and Oncology (R.B., T.K., W.E.B., R.M.M.), University Hospital Muenster, Albert-Schweitzer-Str 33, D-48129 Muenster, Germany; Philips Medical Systems, Hamburg, Germany (H.K.); Bayer Schering Pharma, Berlin, Germany (W.E.); and Interdisciplinary Center for Clinical Research (IZKF Muenster, FG3), University of Muenster, Muenster, Germany (C.B.). From the 2004 RSNA Annual Meeting. Received February 27, 2006; revision requested April 27; revision received July 10; accepted August 7; final version accepted December 4. Supported in part by the German Research Foundation (BR 1653/2-1) and the Federal Ministry of Education and Research, Germany (13N8896). Address correspondence to C.B. (e-mail: bremerc{at}uni-muenster.de).
Purpose: To prospectively investigate steady-state blood volume measurements for early quantitative monitoring of antiangiogenic treatment with ultrasmall superparamagnetic iron oxide (USPIO)–enhanced magnetic resonance (MR) imaging.
Materials and Methods: The institutional animal care committee approved all experiments. HT-1080 fibrosarcoma-bearing nude mice were injected with a thrombogenic vascular targeting agent (VTA) (11 nude mice, 20 tumors) or saline (12 nude mice, 20 tumors). USPIO-enhanced (SH U 555C) MR imaging was performed after the VTA was administered. USPIO-induced changes in tissue R2* (
R2*) were measured with a T2-weighted dual-echo echo-planar imaging sequence, and the vascular volume fraction (VVF) was calculated. Parametric
R2* maps were analyzed with respect to tumor perfusion patterns. Correlative histologic analysis was performed for grading of tissue thrombosis, and tissue perfusion was quantified with fluorescent microbeads. Unpaired Student t test and Spearman nonparametric correlation coefficient were used for statistical analysis.
Results: The
R2* values were significantly (P < .001) reduced shortly after treatment initiation (mean
R2*, 0.017 msec–1 ± 0.0014 [standard error] in control animals vs 0.005 msec–1 ± 0.0007 in animals that received VTA), which was also reflected by a decrease in the VVF (2.47% ± 0.18 vs 0.41% ± 0.48, P < .001). Histologic analysis revealed various degrees of tumor thrombosis after VTA treatment that correlated inversely with the
R2* values (r = –0.83). Moreover, tumor perfusion measurements corroborated the MR results, indicating a significant reduction in tissue perfusion after VTA treatment (mean tissue fluorescence, 570.4 arbitrary units [au] per gram ± 27 vs 161.7 au/g ± 17; P < .05).
Conclusion: USPIO-enhanced MR imaging enables early monitoring of antiangiogenic treatment of tumors.
© RSNA, 2007
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