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Nano and Micro Technologies

Nano and Micro Technologies - Poster Session E

Poster Y19 - Quantitative pH Imaging in MRI - using PMO to control the degradation properties

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Magnetic Resonance Imaging (MRI) is a powerful imaging tool to non - invasively visualize the human body with high temporal and spatial resolution. Although MRI offers many advantages, such as providing detailed anatomical information, excellent tissue penetration, and sensitivity, it is difficult to obtain chemical information. Numerous Bioresponsive contrast agents (CAs) have been reported for visualizing biomarkers such as enzymatic activities, neurotransmitters, metal ions, and extracellular pH (pHe), thereby improving MRI chemical resolution. An essential biomarker, pHe is widely studied due to its relationship with cancer, renal failure and ionic imbalance.

Materials and

Methods:  To quantify pHe using conventional MRI sequence, pH-sensitive CAs are required to modulate the signals obtained (longitudinal relaxation time, T1 or transverse relaxation time, T2) at different pH’s. Our approach is to develop a nucleic acid-based pH responsive MRI contrast agent (CA) using ratiometric technique. Among various nanomaterials, Phosphorodiamidite Morpholino Oligomers (PMO), a nucleic acid analog to DNA, have drawn great attention due to their enhanced stability. Its higher resistance to nucleases compared to DNA makes PMO more effective and reliable for MRI quantification. Additionally, PMOs’ key biosensor characteristics such as high target specificity, chemical versatility, and higher signal quantification make them an ideal candidate for analyzing pH and effective nanoplatforms for quantitative MRI analysis.

Results, Conclusions, and Discussions: In this work, we develop a Gd-based pH-sensitive CAs incorporated into our PMO based pH-MRI CA, based on our previous DNA-based pH CA design, which shortens the T1 time. Additionally, an internal standard CA, Dy-DOTA CA, is incorporated into our PMO as a common T2-weighted CA to serve as an internal standard. The ratiometric pH-responsive MR CA, enhances the T1 signal as pH level decreases, and the signal will be further quantified independently of concentration by using the T2 signal from the Dy – DOTA CA.

Overall, this PMO-based pH MRI CA probe will serve as a versatile platform for sensing biological analytes of interest and provide enhanced chemical information about the body with higher quantification and sensitivity, significantly advances MRI capabilities for precise imaging in clinical research.

Acknowledgements (Optional):