ES-MION-Based Dual-Modality PET/MRI Probes for Acidic Tumor Microenvironment Imaging

Xiuyan Wei; Haitao Zhao; Gang Huang; Jianhua Liu; Weina He; Qingqing Huang

doi:10.1021/acsomega.1c05815

ES-MION-Based Dual-Modality PET/MRI Probes for Acidic Tumor Microenvironment Imaging

ACS Omega. 2022 Jan 18;7(4):3442-3451. doi: 10.1021/acsomega.1c05815. eCollection 2022 Feb 1.

Authors

Xiuyan Wei¹, Haitao Zhao², Gang Huang³, Jianhua Liu¹, Weina He¹, Qingqing Huang³

Affiliations

¹ Medical Chemistry and Bioinformatics Center, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
² Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
³ Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.

Abstract

Among all characteristics of the tumor microenvironment (TME), which are caused by abnormal proliferation of solid tumors, extracellular acidity is an important indicator for malignancy grading. pH-low insertion peptides (pHLIPs) are adopted to discern the acidic TME. To date, different imaging agents including fluorescent, positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance (MR) contrast agents with pHLIPs to target the acidic TME have been used to image various tumor models successfully. In this article, a PET/MRI dual-modality probe, based on extremely small magnetic iron oxide nanoparticles (ES-MIONs) with pHLIPs as a targeting unit, was proposed for the first time. In the phantom study, the probe showed relatively high r ₁ relaxivity (r ₁ = 1.03 mM^-1 s^-1), indicating that it could be used as a T₁-weighted MR contrast agent. The ⁶⁸Ga-radiolabeled probe was further studied in vitro and in vivo to evaluate pHLIP targeting efficacy and feasibility for PET/MRI. PET with intratumoral injection and T₁-weighted MRI with intravenous injection both showed pHLIP-specific delivery of the probe. Therefore, we successfully designed and developed a radiolabeled ES-MION-based dual-modality PET/MRI agent to target the acidic tumor microenvironment. Although the accumulation of the probe in tumors with intravenous injection was not high enough to exhibit signals in the PET imaging study, our study still provides further insights into the ES-MION-based PET/MRI strategy.