PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles

The purpose of this study was to develop a bifunctional iron oxide (IO) nanoparticle probe for PET and MRI scans of tumor integrin α _vβ₃ expression. Methods: Polyaspartic acid (PASP)-coated IO (PASP-IO) nanoparticles were synthesized using a coprecipitation method, and particle size and magnetic properties were measured. A phantom study was used to assess the efficacy of PASP-IO as a T2-weighted MRI contrast agent. PASP-IO nanoparticles with surface amino groups were coupled to cyclic arginine-glycine-aspartic (RGD) peptides for integrin α_vβ₃ targeting and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″,-tetraacetic acid (DOTA) chelators for PET 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/MRI. Results: PASP-IO nanoparticles made by single-step reaction have a core size of 5 nm with a hydrodynamic diameter of 45 ± 10 nm. The saturation magnetization of PASP-IO nanoparticles is about 117 emu/g of iron, and the measured r₂ and r₂* are 105.5 and 165.5 (s·mM)^-1, respectively. A displacement competitive binding assay indicates that DOTA-IO-RGD conjugates bound specifically to integrin α_vβ ₃ in vitro. Both small-animal PET and T2-weighted MRI show integrin-specific delivery of conjugated RGD-PASP-IO nanoparticles and prominent reticuloendothelial system uptake. Conclusion: We have successfully developed an IO-based nanoprobe for simultaneous dual PET and MRI 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. Copyright © 2008 by the Society of Nuclear Medicine, Inc.