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Published online before print June 11, 2007, 10.1148/radiol.2442060371
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(Radiology 2007;244:449-456.)
© RSNA, 2007


Experimental Studies

Antiangiogenic Tumor Treatment: Early Noninvasive Monitoring with USPIO-enhanced MR Imaging in Mice1

Thorsten Persigehl, MD, Ralf Bieker, MD, Lars Matuszewski, MD, Alexander Wall, MD, Torsten Kessler, MD, Hendrik Kooijman, PhD, Norbert Meier, PhD, Wolfgang Ebert, PhD, Wolfgang E. Berdel, MD, Walter Heindel, MD, Rolf M. Mesters, MD, and Christoph Bremer, MD

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* ({Delta}R2*) were measured with a T2-weighted dual-echo echo-planar imaging sequence, and the vascular volume fraction (VVF) was calculated. Parametric {Delta}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 {Delta}R2* values were significantly (P < .001) reduced shortly after treatment initiation (mean {Delta}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 {Delta}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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