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

Title
 Sensitive angiogenesis imaging of orthotopic bladder tumors in mice using a selective magnetic resonance imaging contrast agent containing VEGF121/rGel 
Authors
 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 
Issue Date
2011
Journal Title
 Investigative Radiology 
ISSN
 0020-9996 
Citation
 Investigative Radiology, Vol.46(7) : 441~449, 2011 
Abstract
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/93440
DOI
10.1097/RLI.0b013e3182174fad
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Radiology
Yonsei Authors
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 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00004424-201107000-00005&LSLINK=80&D=ovft
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