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Novel Approaches to Molecular ImagingPET/MRI, MRI and Ultrasound |
1 Stanford University, Stanford, California; 2 Department of Chemistry, Brown University, Providence, Rhode Island
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Objectives: The purpose of this study was to develop a bifunctional iron oxide (IO) nanoparticle probe for positron emission tomography (PET) and magnetic resonance (MR) imaging of tumor integrin
vβ3 expression.
Methods: Poly(aspartic acid)-coated IO nanoparticles (PASP-IO) were synthesized using a co-precipitation method. Particle size and magnetic properties were measured. Phantom study was used to assess the efficacy of PASP-IO as a T2-weighted MR contrast agent. PASP-IO nanoparticles with surface amino groups were coupled to RGD peptides for integrin
vβ3 targeting and macrocyclic DOTA chelator for PET imaging after labeling with 64Cu. IO nanoparticle conjugates were further tested in vitro and in vivo to determine receptor targeting efficacy and feasibility for dual PET/MR imaging.
Results: PASP-IO nanoparticles made by single-step reaction had a core size of 5-7 nm with a hydrodynamic diameter of ~40 nm. The saturation magnetization of PASP-IO nanoparticles was ~117 emu/g Fe. DOTA-IO-RGD conjugates bound specifically to integrin
vβ3 in vitro based on cell binding assay. Both microPET and T2Cu-weighted MR imaging showed integrin-specific delivery of conjugated RGD-PASP-IO nanoparticles and prominent reticuloendothelial system (RES) uptake.
Conclusions: We have successfully developed an iron oxide-based nanoprobe for simultaneous dual PET and MR imaging of tumor integrin expression. The success of this bifunctional imaging approach may allow for earlier tumor detection with a high degree of accuracy and provide further insight into the molecular mechanisms of cancer.
Research Support: NCI: R01-CA119053
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