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

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).

View larger version (161K): [in this window] [in a new window] [Download PPT slide]   Figure 1a: (a, b) Histologic evaluation of the treatment model (HT-1080 fibrosarcoma cells) in the (a) control and (b) treatment groups. (Hematoxylin-eosin stain; objective magnification, x20.) Note the extensive thrombosis seen 4 hours after application of the VTA. (c, d) Corresponding perfusion assay images with fluorescence microbeads show (c) fluorescent microspheres retained in the neovasculature of the tumor in the untreated control specimens, whereas (d) essentially no microspheres can be seen after VTA treatment. (Objective magnification, x20.)

View larger version (174K): [in this window] [in a new window] [Download PPT slide]   Figure 1b: (a, b) Histologic evaluation of the treatment model (HT-1080 fibrosarcoma cells) in the (a) control and (b) treatment groups. (Hematoxylin-eosin stain; objective magnification, x20.) Note the extensive thrombosis seen 4 hours after application of the VTA. (c, d) Corresponding perfusion assay images with fluorescence microbeads show (c) fluorescent microspheres retained in the neovasculature of the tumor in the untreated control specimens, whereas (d) essentially no microspheres can be seen after VTA treatment. (Objective magnification, x20.)

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 1c: (a, b) Histologic evaluation of the treatment model (HT-1080 fibrosarcoma cells) in the (a) control and (b) treatment groups. (Hematoxylin-eosin stain; objective magnification, x20.) Note the extensive thrombosis seen 4 hours after application of the VTA. (c, d) Corresponding perfusion assay images with fluorescence microbeads show (c) fluorescent microspheres retained in the neovasculature of the tumor in the untreated control specimens, whereas (d) essentially no microspheres can be seen after VTA treatment. (Objective magnification, x20.)

View larger version (58K): [in this window] [in a new window] [Download PPT slide]   Figure 1d: (a, b) Histologic evaluation of the treatment model (HT-1080 fibrosarcoma cells) in the (a) control and (b) treatment groups. (Hematoxylin-eosin stain; objective magnification, x20.) Note the extensive thrombosis seen 4 hours after application of the VTA. (c, d) Corresponding perfusion assay images with fluorescence microbeads show (c) fluorescent microspheres retained in the neovasculature of the tumor in the untreated control specimens, whereas (d) essentially no microspheres can be seen after VTA treatment. (Objective magnification, x20.)

View larger version (5K): [in this window] [in a new window] [Download PPT slide]   Figure 2a: Graphs show quantitative data used to analyze the effects of antiangiogenic treatment. Note that VTA treatment resulted in a significant reduction (*) of (a) the R2* (control group, 20 tumors; VTA group, 20 tumors) and (b) the VVF (control group, 20 tumors; VTA group, 20 tumors) values. (c) Moreover, results of a perfusion assay with fluorescent microbeads corroborated the MR results and showed a 72% reduction in tumor perfusion after VTA treatment (control group, three tumors; VTA group, four tumors). In a–c, data are mean values and error bars indicate standard error of the mean. (d) Morphometric analysis revealed an inverse correlation of the grade of tumor thrombosis and/or necrosis with the R2* (, r = –0.83) and the VVF (, r = –0.74) values.

View larger version (5K): [in this window] [in a new window] [Download PPT slide]   Figure 2b: Graphs show quantitative data used to analyze the effects of antiangiogenic treatment. Note that VTA treatment resulted in a significant reduction (*) of (a) the R2* (control group, 20 tumors; VTA group, 20 tumors) and (b) the VVF (control group, 20 tumors; VTA group, 20 tumors) values. (c) Moreover, results of a perfusion assay with fluorescent microbeads corroborated the MR results and showed a 72% reduction in tumor perfusion after VTA treatment (control group, three tumors; VTA group, four tumors). In a–c, data are mean values and error bars indicate standard error of the mean. (d) Morphometric analysis revealed an inverse correlation of the grade of tumor thrombosis and/or necrosis with the R2* (, r = –0.83) and the VVF (, r = –0.74) values.

View larger version (6K): [in this window] [in a new window] [Download PPT slide]   Figure 2c: Graphs show quantitative data used to analyze the effects of antiangiogenic treatment. Note that VTA treatment resulted in a significant reduction (*) of (a) the R2* (control group, 20 tumors; VTA group, 20 tumors) and (b) the VVF (control group, 20 tumors; VTA group, 20 tumors) values. (c) Moreover, results of a perfusion assay with fluorescent microbeads corroborated the MR results and showed a 72% reduction in tumor perfusion after VTA treatment (control group, three tumors; VTA group, four tumors). In a–c, data are mean values and error bars indicate standard error of the mean. (d) Morphometric analysis revealed an inverse correlation of the grade of tumor thrombosis and/or necrosis with the R2* (, r = –0.83) and the VVF (, r = –0.74) values.

View larger version (11K): [in this window] [in a new window] [Download PPT slide]   Figure 2d: Graphs show quantitative data used to analyze the effects of antiangiogenic treatment. Note that VTA treatment resulted in a significant reduction (*) of (a) the R2* (control group, 20 tumors; VTA group, 20 tumors) and (b) the VVF (control group, 20 tumors; VTA group, 20 tumors) values. (c) Moreover, results of a perfusion assay with fluorescent microbeads corroborated the MR results and showed a 72% reduction in tumor perfusion after VTA treatment (control group, three tumors; VTA group, four tumors). In a–c, data are mean values and error bars indicate standard error of the mean. (d) Morphometric analysis revealed an inverse correlation of the grade of tumor thrombosis and/or necrosis with the R2* (, r = –0.83) and the VVF (, r = –0.74) values.

View larger version (44K): [in this window] [in a new window] [Download PPT slide]   Figure 3a: (a, b) Anatomic and (c, d) parametric MR images of HT-1080 xenografts. Tumor xenografts were implanted bilaterally into flanks of nude mice. Tumors are clearly delineated in a and b high-spatial-resolution T2-weighted images. USPIO-enhanced (SH U 555C) MR imaging was performed 4 hours after injection of (a, c) saline or (b, d) VTA. (c, d) Parametric R2* maps representing individual tumor sections of highly vascularized (c) untreated and (d) VTA-treated fibrosarcoma reveal excellent response to thrombogenic VTA.

View larger version (56K): [in this window] [in a new window] [Download PPT slide]   Figure 3b: (a, b) Anatomic and (c, d) parametric MR images of HT-1080 xenografts. Tumor xenografts were implanted bilaterally into flanks of nude mice. Tumors are clearly delineated in a and b high-spatial-resolution T2-weighted images. USPIO-enhanced (SH U 555C) MR imaging was performed 4 hours after injection of (a, c) saline or (b, d) VTA. (c, d) Parametric R2* maps representing individual tumor sections of highly vascularized (c) untreated and (d) VTA-treated fibrosarcoma reveal excellent response to thrombogenic VTA.

View larger version (32K): [in this window] [in a new window] [Download PPT slide]   Figure 3c: (a, b) Anatomic and (c, d) parametric MR images of HT-1080 xenografts. Tumor xenografts were implanted bilaterally into flanks of nude mice. Tumors are clearly delineated in a and b high-spatial-resolution T2-weighted images. USPIO-enhanced (SH U 555C) MR imaging was performed 4 hours after injection of (a, c) saline or (b, d) VTA. (c, d) Parametric R2* maps representing individual tumor sections of highly vascularized (c) untreated and (d) VTA-treated fibrosarcoma reveal excellent response to thrombogenic VTA.

View larger version (42K): [in this window] [in a new window] [Download PPT slide]   Figure 3d: (a, b) Anatomic and (c, d) parametric MR images of HT-1080 xenografts. Tumor xenografts were implanted bilaterally into flanks of nude mice. Tumors are clearly delineated in a and b high-spatial-resolution T2-weighted images. USPIO-enhanced (SH U 555C) MR imaging was performed 4 hours after injection of (a, c) saline or (b, d) VTA. (c, d) Parametric R2* maps representing individual tumor sections of highly vascularized (c) untreated and (d) VTA-treated fibrosarcoma reveal excellent response to thrombogenic VTA.