期刊
FASEB JOURNAL
卷 22, 期 12, 页码 4179-4189出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.08-112060
关键词
magnetic resonance imaging; fumagillin; cancer; molecular imaging; antiangiogenic
资金
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- National Institute of Biomedical Imaging and BioEngineering [HL-78631, HL-73646, CA-119342]
Our objectives were 1) to characterize angiogenesis in the MDA-MB-435 xenograft mouse model with three-dimensional (3D) MR molecular imaging using alpha(5)beta(1)(RGD)- or irrelevant RGS-targeted paramagnetic nanoparticles and 2) to use MR molecular imaging to assess the antiangiogenic effectiveness of alpha(5)beta(1)(alpha(v)beta(3))- vs. alpha(v)beta(3)-targeted fumagillin (50 mu g/kg) nanoparticles. Tumor-bearing mice were imaged with MR before and after administration of either alpha(5)beta(1)(RGD) or irrelevant RGS-paramagnetic nanoparticles. In experiment 2, mice received saline or alpha(5)beta(1)(alpha(v)beta(3))- or alpha(v)beta(3)-targeted fumagillin nanoparticles on days 7, 11, 15, and 19 posttumor implant. On day 22, MRI was performed using alpha(5)beta(1)(alpha(v)beta(3))-targeted paramagnetic nanoparticles to monitor the antiangiogenic response. 3D reconstructions of alpha(5)beta(1)(RGD)-signal enhancement revealed a sparse, asymmetrical pattern of angiogenesis along the tumor periphery, which occupied < 2.0% tumor surface area. alpha(5)beta(1)-targeted rhodamine nanoparticles colocalized with FITC-lectin corroborated the peripheral neovascular signal. alpha(5)beta(1)(alpha(v)beta(3))-fumagillin nanoparticles decreased neovasculature to negligible levels relative to control; alpha(v)beta(3)-targeted fumagillin nanoparticles were less effective (P > 0.05). Reduction of angiogenesis in MDA-MB-435 tumors from low to negligible levels did not decrease tumor volume. MR molecular imaging may be useful for characterizing tumors with sparse neovasculature that are unlikely to have a reduced growth response to targeted antiangiogenic therapy.
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