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Rapid Accumulation and Internalization of Radiolabeled Herceptin in an Inflammatory Breast Cancer Xenograft with Vasculogenic Mimicry Predicted by the Contrast-enhanced Dynamic MRI with the Macromolecular Contrast Agent G6-(1B4M-Gd)₂₅₆

Hitachi Medical Co. Chaired Departments of Diagnostic and Interventional Imagiology [H. K., S. K., K. T.] and Nuclear Medicine and Diagnostic Imaging [T. S., N. S., A. H., J. K.], Kyoto 606-8507, Japan; Pharmacology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan [K. S., I. W., Y. H., H. W.]; and Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892 [M. W. B.]

The rapid blood flow and perfusion of macromolecules in the inflammatory breast cancer xenograft (WIBC-9), which exhibits a "vasculogenic mimicry" type of angiogenesis without the participation of endothelial cells and expresses high levels of the HER-2/neu antigen, was evaluated in mice using 3D-micro-MR angiography using a novel macromolecular MR contrast agent [G6-(1B4M-Gd)₂₅₆]. Herceptin, which recognizes the HER-2/neu antigen and has similar size (10 nm) to G6-(1B4M-Gd)₂₅₆, accumulated and internalized in the WIBC-9 tumors more quickly than in the control MC-5 tumors that progress with normal angiogenesis. Three dimensional micro-MRI with the G6-(1B4M-Gd)₂₅₆ macromolecular MRI contrast agent distinguishes between the different types of angiogenesis and is predictive of the rapid accumulation and internalization of Herceptin in the WIBC-9 inflammatory breast cancer xenograft.

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