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 U,133 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 alpha(v)beta(3) targeting and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N '',N',-tetraacetic acid (DOTA) chelators for PET after labeling with Cu-64. 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 r(2) and r(2)* 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 alpha(v)beta(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.