Molecular magnetic resonance imaging approaches used to aid in the understanding of angiogenesis in vivo: implications for tissue engineering.
In tissue engineering it is often necessary to assess angiogenesis associated with engineered tissue grafts. The levels of vascular endothelial growth factor receptor 2 (VEGF-R2) is elevated during angiogenesis. The goal of this study was to develop and assess a novel magnetic resonance imaging (MRI) molecular probe for the in vivo detection of VEGF-R2 in an experimental rodent model of disease. The possible use of the probe in tissue engineering applications is discussed. The molecular targeting agent we used in our study incorporated a magnetite-based dextran-coated nanoparticle backbone covalently bound to an anti-VEGF-R2 antibody. We used molecular MRI with an anti-VEGF-R2 probe to detect in vivo VEGF-R2 levels as a molecular marker for gliomas (primary brain tumors). Tumor regions were compared with normal tissue. Nonimmune nonspecific normal rat immunoglobulin G coupled to the dextran-coated nanoparticles was used as a control. Prussian blue staining for iron-based nanoprobes was used to confirm the specificity of the probe for VEGF-R2 in glioma tissue. VEGF-R2 levels in tumor tissues were also confirmed in western blots and via immunohistochemistry. Based on our results, in vivo evaluation of tissue angiogenesis using molecular MRI is possible in tissue engineering applications.
Towner
Rheal A
RA
Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA. rheal-towner@omrf.org
Smith
Nataliya
N
Asano
Yasuko
Y
He
Ting
T
Doblas
Sabrina
S
Saunders
Debra
D
Silasi-Mansat
Robert
R
Lupu
Florea
F
Seeney
Charles E
CE
D000818:Animals; D003432:Cross-Linking Reagents / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D051381:Rats; D011916:Rats, Inbred F344; D023822:Tissue Engineering / Q000379:methods*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D003432:Cross-Linking Reagents; D005290:Ferric Compounds; D015335:Molecular Probes; C000499:ferric oxide; D040301:Vascular Endothelial Growth Factor Receptor-2