In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles

Yunkai Zhu,Wenbin Guan,Zhongyang Zhang,Weiyong Liu,Ying Sun,Yaqing Chen,Ying Sun,Yourong Duan,Yourong Duan,Yourong Duan,Ying Sun,Jun Jiang

doi:10.3390/ijms16059573

Yunkai Zhu, Wenbin Guan + Show 10 more

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https://doi.org/10.3390/ijms16059573

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The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.

Highlights

Prostate cancer (PCa) is the most common malignancy affecting men in the Western world [1].Transrectal ultrasound, magnetic resonance imaging (MRI), and nuclear medicine is currently used in PCa imaging [2]
Inverted microscope demonstrated that the polypeptide-superparamagnetic iron oxide nanoparticles (SPIONs) exhibited a smooth and uniform spherical morphology (Figure 1A)
The VSM results confirmed the superparamagnetic characteristic of polypeptide-SPIONs (Figure 1D)

Summary

Introduction

Transrectal ultrasound, magnetic resonance imaging (MRI), and nuclear medicine is currently used in PCa imaging [2]. As current imaging modalities provide limited functional information of PCa, the sensitivity of these imaging modalities remains relatively poor [3], leading to under-treatment of the aggressive disease. The presence of chronic prostatitis is often indistinguishable from PCa lesions with current imaging modalities [4], subsequently resulting in unnecessary biopsies [5]. Improvements in current imaging modalities are urgently needed. Molecular imaging enables the visualization of tumor-specific biomarkers involved in the development and progression of tumors [6]. By designing imaging probes offering specific bindings with tumor biomarkers, tumor lesions could be detected in their early stages. The accuracy of PCa imaging might be significantly improved with molecular imaging

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