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, Jinsuck Suh, Seungjoo Haam, Michael G. Rosenblum, yongmin Huh

Research output: Contribution to journalArticle

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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

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Urinary Bladder Neoplasms
Nanoparticles
Contrast Media
Vascular Endothelial Growth Factor A
Magnetic Resonance Imaging
Neoplasms
manganese ferrite
Phosphorylation
Blood Vessels
Tail
Veins
Electron Microscopy
Urinary Bladder
Fluorescence
Injections
Water

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Cho, Eun Jin ; Yang, Jaemoon ; Mohamedali, Khalid A. ; Lim, Eun Kyung ; Kim, Eun Jung ; Farhangfar, Carol J. ; Suh, Jinsuck ; Haam, Seungjoo ; Rosenblum, Michael G. ; Huh, yongmin. / Sensitive angiogenesis imaging of orthotopic bladder tumors in mice using a selective magnetic resonance imaging contrast agent containing VEGF 121/rGel. In: Investigative Radiology. 2011 ; Vol. 46, No. 7. pp. 441-449.
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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.",
author = "Cho, {Eun Jin} and Jaemoon Yang and Mohamedali, {Khalid A.} and Lim, {Eun Kyung} and Kim, {Eun Jung} and Farhangfar, {Carol J.} and Jinsuck Suh and Seungjoo Haam and Rosenblum, {Michael G.} and yongmin Huh",
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Sensitive angiogenesis imaging of orthotopic bladder tumors in mice using a selective magnetic resonance imaging contrast agent containing VEGF 121/rGel. / Cho, Eun Jin; Yang, Jaemoon; Mohamedali, Khalid A.; Lim, Eun Kyung; Kim, Eun Jung; Farhangfar, Carol J.; Suh, Jinsuck; Haam, Seungjoo; Rosenblum, Michael G.; Huh, yongmin.

In: Investigative Radiology, Vol. 46, No. 7, 01.07.2011, p. 441-449.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sensitive angiogenesis imaging of orthotopic bladder tumors in mice using a selective magnetic resonance imaging contrast agent containing VEGF 121/rGel

AU - Cho, Eun Jin

AU - Yang, Jaemoon

AU - Mohamedali, Khalid A.

AU - Lim, Eun Kyung

AU - Kim, Eun Jung

AU - Farhangfar, Carol J.

AU - Suh, Jinsuck

AU - Haam, Seungjoo

AU - Rosenblum, Michael G.

AU - Huh, yongmin

PY - 2011/7/1

Y1 - 2011/7/1

N2 - 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.

AB - 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.

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