In vivo maps of extracellular pH in murine melanoma by CEST-MRI
D Delli Castelli1, Giuseppe Ferrauto, Juan Carlos Cutrin
1Department of Molecular Biotechnology and Health Sciences, Molecular Imaging Center, University of Torino, Italy.
Purpose:
A novel method based on the use of Yb-HPDO3A as MRI Para-CEST agent for in vivo pH mapping of the tumor region in a melanoma murine model is reported. This method does not require the knowledge of the concentration of the imaging agent.
Methods:
C57BL/6-mice were inoculated with B16-F10 cells. CEST-MR images of tumor and bladder were acquired upon the i.v. administration of Yb-HPDO3A (1.2 mmol/Kg). pH was assessed by the use of a ratiometric method.
Results:
Yb-HPDO3A distributes well in the extracellular space of the tumor allowing the detection of good levels of saturation transfer (ST). It is excreted throughout kidneys and accumulated in the bladder thus yielding a strong CEST signal from urine. By comparing the ST% obtained upon selective irradiation of the two OH resonances belonging to the two isomeric forms of Yb-HPDO3A, it has been possible to measure the extracellular pH for each voxel (0.22 mm(3) ). The obtained pH-maps of tumors show a great heterogeneity. Marked differences are associated to tumor staging.
Conclusion:
The application of Yb-HPDO3A to measure extracellular tumor pH provides a good spatio-temporal resolution and it does not require the prior knowledge of the contrast agent concentration. The herein reported data support the potential clinical translation of Yb-HPDO3A.
Insights
This study introduces Ytterbium-HPDO3A (Yb-HPDO3A) for MRI pH mapping in melanoma tumors. The novel method accurately measures extracellular tumor pH with high resolution, without needing to know the contrast agent concentration.
Area of Science:
- Biomedical Imaging
- Magnetic Resonance Imaging (MRI)
- Contrast Agents
Background:
- Accurate in vivo pH mapping is crucial for understanding tumor microenvironments and staging.
- Current MRI contrast agents often require knowledge of concentration, limiting their clinical application.
- Developing novel agents for accurate, concentration-independent pH mapping is an unmet clinical need.
Purpose of the Study:
- To report a novel method for in vivo pH mapping of tumor regions using Ytterbium-HPDO3A (Yb-HPDO3A) as a para-CEST MRI agent.
- To demonstrate that this method does not require prior knowledge of the imaging agent's concentration.
- To assess the potential clinical translation of Yb-HPDO3A for tumor pH measurement.
Main Methods:
- A melanoma murine model (C57BL/6 mice inoculated with B16-F10 cells) was used.
- Contrast-enhanced chemical exchange saturation transfer (CEST) MRI images of tumors and bladders were acquired after intravenous administration of Yb-HPDO3A.
- Extracellular pH was assessed using a ratiometric method based on the saturation transfer (ST) of Yb-HPDO3A's hydroxyl resonances.
Main Results:
- Yb-HPDO3A effectively distributed in the tumor's extracellular space, enabling good saturation transfer (ST) detection.
- The agent was excreted via kidneys and accumulated in the bladder, producing a strong CEST signal from urine.
- Comparison of ST% from isomeric Yb-HPDO3A hydroxyl resonances allowed for voxel-wise extracellular pH measurement (0.22 mm³).
- Tumor pH maps revealed significant heterogeneity and differences related to tumor staging.
Conclusions:
- Yb-HPDO3A enables extracellular tumor pH measurement with good spatio-temporal resolution.
- The method's independence from contrast agent concentration is a significant advantage.
- The findings support the potential clinical translation of Yb-HPDO3A for tumor pH assessment.
