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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Extracellular acidity in the tumor microenvironment (TME) is a key indicator of malignancy.
• pH-low insertion peptides (pHLIPs) are effective in targeting acidic TME.
• Current imaging agents for acidic TME include fluorescent, PET, SPECT, and MR contrast agents.

Purpose of the Study:

• To develop and evaluate a novel dual-modality positron emission tomography (PET) and magnetic resonance imaging (MRI) probe for targeting the acidic tumor microenvironment.
• To utilize extremely small magnetic iron oxide nanoparticles (ES-MIONs) functionalized with pHLIPs as a targeting agent.
• To assess the probe's performance in phantom, in vitro, and in vivo studies.

Main Methods:

• Design and synthesis of a dual-modality PET/MRI probe based on ES-MIONs conjugated with pHLIPs.
• Characterization of the probe's relaxivity for MRI contrast agent potential.
• Radiolabeling of the probe with Gallium-68 (⁶⁸Ga) for PET imaging.
• In vitro and in vivo evaluation of pHLIP targeting efficacy and biodistribution.

Main Results:

• The probe exhibited high r1 relaxivity (1.03 mM^-1 s^-1), suitable for T₁-weighted MRI.
• PET imaging with intratumoral injection and T₁-weighted MRI with intravenous injection confirmed pHLIP-specific delivery to tumors.
• While PET signal accumulation was limited with intravenous injection, the study validated the ES-MION-based PET/MRI strategy.

Conclusions:

• A novel radiolabeled ES-MION-based dual-modality PET/MRI agent was successfully developed for targeting acidic tumor microenvironments.
• The probe demonstrated pHLIP-specific targeting and potential as an MRI contrast agent.
• Further optimization is needed for enhanced PET imaging sensitivity with intravenous administration, but the strategy shows promise for TME imaging.