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Dynamic contrast-enhanced CEST MRI using a low molecular weight dextran.

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|November 15, 2021
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Summary
This summary is machine-generated.

This study introduces dextran (Dex1) as a novel, biocompatible chemical exchange saturation transfer (CEST) MRI contrast agent. Dex1 effectively enhances tumor visualization in brain cancer models, showing promising potential for clinical translation.

Keywords:
CESTMRIbrain tumordextranpermeability

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Area of Science:

  • Biomedical Imaging
  • Magnetic Resonance Imaging
  • Biomaterials

Background:

  • Chemical Exchange Saturation Transfer (CEST) MRI offers a promising avenue for developing biocompatible contrast agents.
  • Sugars, particularly dextrans, present potential as effective and translatable CEST agents due to their biocompatibility.

Purpose of the Study:

  • To develop and evaluate the smallest clinically available dextran form, Dex1 (1 kDa), as a novel CEST MRI contrast agent.
  • To assess the in vitro and in vivo performance of Dex1 for detecting brain tumors and evaluating tumor hemodynamics.

Main Methods:

  • In vitro characterization of Dex1's CEST properties at 11.7T, identifying a CEST signal at ~1.2 ppm.
  • In vivo CEST MRI studies in C57BL6 mice with orthotopic GL261 brain tumors using a 11.7T scanner.
  • Acquisition of steady-state Z-spectral and dynamic dextran-enhanced (DDE) images before and after Dex1 injection.

Main Results:

  • Dex1 demonstrated a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons.
  • Significantly higher CEST contrast enhancement was observed in tumors compared to contralateral brain tissue (∆MTRasym1.2 ppm = 0.010 ± 0.006 vs. 0.002 ± 0.008, P = 0.0069).
  • Pharmacokinetic analysis revealed significantly higher Dex1 uptake in tumors (AUC[0-10 min] = 21.9 ± 4.2 %·min) than in normal brain tissue (5.3 ± 6.4 %·min, P = 0.0294) in tumor-bearing mice, with no uptake in non-tumor-bearing mice.

Conclusions:

  • Dex1 serves as a novel and effective CEST MRI contrast agent with potential for clinical translation.
  • The study demonstrates Dex1's capability to enhance tumor visualization and assess tumor hemodynamics, consistent with DCE MRI and fluorescence microscopy findings.
  • Dex1 represents a promising, biocompatible agent for advanced MRI-based tumor diagnostics.