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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 αvβ3 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 αvβ3 integrin. After being incubated with αvβ3 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 αvβ3 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.

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

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