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The purpose of this study was to 1) noninvasively monitor the response to anti\u2010PDGFR treatment, and 2) understand the underlying mechanism of this response. Thus, response to treatment was studied in a prostate cancer bone metastasis model using macromolecular (biotin\u2013bovine serum albumin [BSA]\u2013Gd\u2010diethylene triamine pentaacetic acid [GdDTPA]) dynamic contrast\u2010enhanced magnetic resonance imaging (DCE\u2010MRI). Human prostate cancer (PC\u20103MM2) bone metastases that caused osteolysis and grew in neighboring muscle showed a high blood\u2010volume fraction (fBV) and vascular permeability (PS) at the tumor periphery compared to muscle tissue and intraosseous tumor. Imatinib alone or with paclitaxel significantly reduced PS by 35% (one\u2010tailed paired <jats:italic>t<\/jats:italic>\u2010test, <jats:italic>P<\/jats:italic> = 0.045) and 40% (<jats:italic>P<\/jats:italic> = 0.0003), respectively, whereas paclitaxel alone or no treatment had no effect. Based on changes in PS, we hypothesized that imatinib interferes with the signaling pathway of vascular endothelial growth factor (VEGF). This mechanism was verified by immunohistochemistry. It demonstrated reduced activation of both PDGFR\u2010\u03b2 and VEGF receptor 2 (VEGFR2) in imatinib\u2010treated mice. Our study therefore demonstrates that macromolecular DCE\u2010MRI can be used to detect early vascular effects associated with response to therapy targeted to PDGFR, and provides insight into the role played by VEGF in anti\u2010PDGFR therapy. Magn Reson Med 60:822\u2013833, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mrm.21727","type":"journal-article","created":{"date-parts":[[2008,9,25]],"date-time":"2008-09-25T08:08:23Z","timestamp":1222330103000},"page":"822-833","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Macromolecular dynamic contrast\u2010enhanced (DCE)\u2010MRI detects reduced vascular permeability in a prostate cancer bone metastasis model following anti\u2013platelet\u2010derived growth factor receptor (PDGFR) therapy, indicating a drop in vascular endothelial growth factor receptor (VEGFR) activation"],"prefix":"10.1002","volume":"60","author":[{"given":"Hagit","family":"Dafni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun\u2010Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James 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