Noninvasively characterizing the different αvβ3 expression patterns in lung cancers with RGD-USPIO using a clinical 3.0T MR scanner

Tao Jiang^1,*, Chunfu Zhang², Xuan Zheng^3,*, Xiongfei Xu⁴, Xuan Xie², Hongchao Liu¹, Shiyuan Liu¹

¹Department of Radiology, ChangZheng Hospital Affiliated to Second Military Medical University, 415 Fengyang Road, Shanghai, China; ²Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China; ³Department of Nutrition, Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China; ⁴Department of Immunology, Second Military Medical University, Shanghai, China; *These authors contributed equally to this work

Abstract: The adhesion molecule αvβ3 integrin plays an important role in tumor development and metastases. We demonstrated the specificity of the probe to αvβ3 integrin with transmission electron microcopy (TEM) and magnetic resonance imaging (MRI). The in vivo targeting behavior of the probe was examined in 2 tumor models with different αvβ3 expression patterns by a 3.0T MRI scanner. MR imaging showed that R2* pseudo-color pictures of A549 lung cancer tumor was different from that of 3LL lung cancer. For A549 tumor, an homogeneous decrease of signal intensity was observed throughout the tumor, which was more evident in the periphery or central areas. Histological studies revealed that αvβ3 integrin was expressed both on the tumor vessel and tumor cells for A549 tumor. Our findings indicated that it was possible to noninvasively characterize the different αvβ3 expression pattern in lung cancers with arginine-glycine-aspartic acid (RGD) peptide conjugated ultra-small superparamagnetic iron oxide nanoparticles (RGD-USPIO) using a clinical 3.0T MR scanner. Nevertheless, the way of imaging targeting presentation of the probe differed in tumors with different αvβ3 expression patterns.

Keywords: USPIO, RGD peptide, αvβ3 integrin, MR molecular imaging