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A DNA-Based MRI Contrast Agent for Quantitative pH Measurement.

Hyewon Seo1, Kristine Y Ma1, Erin E Tuttle2

  • 1Department of Bioengineering, Northeastern University, Boston, Massachusetts 02115, United States.

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|February 24, 2021
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Summary

Researchers developed a novel DNA-based MRI contrast agent for quantitative extracellular pH measurement. This new method offers accurate and reproducible pH imaging for various disease applications.

Keywords:
DNA dendrimerDNA nanostructureMRI contrast agentbioimagingpH quantification

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Area of Science:

  • Biomedical Imaging
  • Nanotechnology
  • Molecular Biology

Background:

  • Extracellular pH is a critical biomarker for cell metabolism and disease progression.
  • Current MRI methods for pH quantification have limitations, especially with nanoparticle agents.
  • Existing nanoparticle agents often yield qualitative rather than quantitative pH results due to heterogeneity.

Purpose of the Study:

  • To develop a novel, quantitative, and reproducible DNA-based MRI contrast agent for extracellular pH measurement.
  • To establish a relaxometric model for pH quantification using the developed agent.
  • To validate the MRI-based pH assessment against traditional methods.

Main Methods:

  • Developed a dendritic DNA scaffold functionalized with pH-responsive MRI-sensitive constructs (Gd(NP-DO3A)).
  • Evaluated the r1 and r2 response of the pH-DMRCA across a pH range of 5-9.
  • Validated MRI-based pH measurements against pH electrode measurements in multiple samples and human blood plasma.

Main Results:

  • Established a reliable relaxometric model for pH quantification.
  • Demonstrated a strong linear correlation (R2 = 0.99) between MRI-based and electrode-measured pH.
  • Confirmed concentration-independence and validated the method in human blood plasma.

Conclusions:

  • The novel DNA-based MRI contrast agent (pH-DMRCA) enables accurate and reproducible quantitative extracellular pH imaging.
  • This method overcomes limitations of previous nanoparticle agents and offers potential for various disease applications.
  • The versatility of DNA nanostructures allows for broad applicability in imaging diseases where extracellular pH is a key indicator.