MR molecular imaging and fluorescence microscopy for identification of activated tumor endothelium using a bimodal lipidic nanoparticle

作者：Mulder WJM^*; Strijkers GJ; Habets JW; Bleeker EJW; van der Schaft DWJ; Storm G; Koning GA; Griffioen AW; Nicolay K

来源：The FASEB Journal, 2005, 19(12): 2008-+.

DOI：10.1096/fj.05-4145fjc

• paramagnetic liposomes
• RGD peptide
• alpha v beta 3-integrin
• angiogenesis
• tumor bearing mice

In oncological research, there is a great need for imaging techniques that specifically identify angiogenic blood vessels in tumors on the basis of differences in the expression level of biomolecular markers. In the angiogenic cascade, different cell surface receptors, including the alpha v beta 3-integrin, are strongly expressed on activated endothelial cells. In the present study, we aimed to image angiogenesis by detecting the expression of alpha v beta 3 in tumor bearing mice with a combination of magnetic resonance imaging (MRI) and fluorescence microscopy. To that end, we prepared MR-detectable and fluorescent liposomes, which carry similar to 700 alpha v beta 3-specific RGD peptides per liposome. RGD competition experiments and RAD-conjugated liposomes were used as controls for specificity. In vivo, both RAD liposomes and RGD liposomes gave rise to signal increase on T-1-weighted MR images. It was established by the use of ex vivo fluorescence microscopy that RGD liposomes and RAD liposomes accumulated in the tumor by different mechanisms. RGD liposomes were specifically associated with activated tumor endothelium, while RAD liposomes were located in the extravascular compartment. This study demonstrates that MR molecular imaging of angiogenesis is feasible by using a targeted contrast agent specific for the alpha v beta 3-integrin, and that the multimodality imaging approach gave insight into the exact mechanism of accumulation in the tumor.

• 出版日期2005-10