Feasibility of USPIOs for T1-weighted MR molecular imaging of tumor receptors

Abstract

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles have been extensively explored for T₂- and T₁-weighted magnetic resonance imaging (MRI). However, whether USPIOs could be simultaneously used for T₂- and T₁-weighted MR tumor receptor imaging is seldom reported. Therefore, in the current study, SPECT/MRI dual-functional probes targeting α_vβ₃ integrin receptors was developed based on USPIOs to examine the feasibility of T₂- and T₁-weighted dual MRI of tumor receptors. The probes were around 4.5 nm, had superior T₁ and T₂ MRI contrast effects in water suspensions and high specificity for α_vβ₃ integrin. After being incubated with α_vβ₃ positive tumor cells, MR imaging of cell suspensions indicated that the T₂ contrast effect of the probe was pronounced and enhanced compared to that in water suspensions at the same concentration, while the T₁ contrast effect vanished. After being intravenously administered into tumor bearing mice, the probes could specifically accumulate in tumors as revealed by SPECT/CT imaging. T₂-Weighted MRI showed a hypo-intense signal in the tumor region and the signal intensity enhanced with prolongation of time, while for T₁-weighted MRI, no hyper-intense signal was observed in the same tumor area. Transmission electron microscopy of tumor tissues revealed that the probes aggregated in cell organelles after targeting α_vβ₃ integrin. Our study suggested that USPIOs with both superior T₁ and T₂ contrast effects could only be used for T₂-weighted, but not for T₁-weighted MR tumor receptor imaging due to aggregation of the particles in cell organelles.