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Sensitive angiogenesis imaging of orthotopic bladder tumors in mice using a selective magnetic resonance imaging contrast agent containing VEGF121/rGel

 Eun-Jin Cho  ;  Jaemoon Yang  ;  Yong-Min Huh  ;  Michael G. Rosenblum  ;  Seungjoo Haam  ;  Jin-Suck Suh  ;  Carol J. Farhangfar  ;  Eun-Jung Kim  ;  Eun-Kyung Lim  ;  Khalid A. Mohamedali 
 Investigative Radiology, Vol.46(7) : 441-449, 2011 
Journal Title
 Investigative Radiology 
Issue Date
OBJECTIVES: To investigate the efficiency of magnetic resonance imaging (MRI) contrast agents employing vascular endothelial growth factor (VEGF121)/rGel conjugated MnFe2O4 nanocrystals for imaging of neovasculature using a bladder tumor model. MATERIALS AND METHODS: VEGF121/rGel was conjugated to MnFe2O4 nanoparticles (MNPs). The targeting efficiency and detection capability of the VEGF121/rGel-MNPs were investigated in both KDR-deficient (253JB-V) and KDR-overexpressing (PAE/KDR) cells using MRI. The internalization of VEGF121/rGel-MNPs into cells was confirmed by electron microscopy. Their phosphorylation ability and cytotoxicity were compared with unconjugated VEGF121/rGel. The orthotopic tumor mice were established by implanting low KDR-expressing 253JB-V cells into the bladder dome. After tail-vein injection of VEGF121/rGel-MNPs, the MR signal enhancement of intratumoral vessels by VEGF121/rGel-MNPs was observed and inhibition test using VEGF121 was also conducted. Ex vivo MR imaging of tumor tissue, and a fluorescence immunostaining study was also performed. RESULTS: The water-soluble VEGF121/rGel-MNPs (44.5 ± 1.2 nm) were stably suspended in the biologic media and exhibited a high relaxivity coefficient (423 mMs). They demonstrated sufficient targeting capability against KDR-overexpressing PAE/KDR cells, as confirmed by dose-dependent MR images and VEGF121 inhibition tests. The phosphorylation activity of KDR and cytotoxicity of VEGF121/rGel-MNPs were evaluated. VEGF121/rGel-MNPs successfully targeted the tumor and provided accurate anatomic details through (i) acquisition of clear neoangiogenic vascular distributions and (ii) obvious enhancement of the MR signal in T2*-weighted images. Immunostaining and blocking studies demonstrated the specific targeting ability of VEGF121/rGel-MNPs toward intratumoral angiogenesis. CONCLUSIONS: Synthesized VEGF121/rGel-MNPs as targeted MR imaging contrast agents can be specifically delivered to tumors and bind to KDR-expressing angiogenic tumor vessels.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실)
Yonsei Authors
서진석(Suh, Jin Suck) ; 양재문(Yang, Jae Moon) ; 허용민(Huh, Yong Min)
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