Sensitive angiogenesis imaging of orthotopic bladder tumors in mice using a selective magnetic resonance imaging contrast agent containing VEGF 121/rGel

Eun Jin Cho, Jaemoon Yang, Khalid A. Mohamedali, Eun Kyung Lim, Eun Jung Kim, Carol J. Farhangfar, Jin Suck Suh, Seungjoo Haam, Michael G. Rosenblum, Yong Min Huh

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objectives: To investigate the efficiency of magnetic resonance imaging (MRI) contrast agents employing vascular endothelial growth factor (VEGF 121)/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 mM-1s-1). They demonstrated sufficient targeting capability against KDR-overexpressing PAE/KDR cells, as confirmed by dosedependent 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 VEGF 121/rGel-MNPs as targeted MR imaging contrast agents can be specifically delivered to tumors and bind to KDR-expressing angiogenic tumor vessels.

Original languageEnglish
Pages (from-to)441-449
Number of pages9
JournalInvestigative Radiology
Volume46
Issue number7
DOIs
Publication statusPublished - 2011 Jul 1

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

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