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

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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 r1 relaxivity (r1 = 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.

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Wei, X., Zhao, H., Huang, G., Liu, J., He, W., & Huang, Q. (2022). ES-MION-Based Dual-Modality PET/MRI Probes for Acidic Tumor Microenvironment Imaging. ACS Omega, 7(4), 3442–3451. https://doi.org/10.1021/acsomega.1c05815

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