Development of a Nanoscale Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agent That...

Area of Science:

• Biomedical Imaging
• Nanotechnology
• Chemical Engineering

Background:

• AcidoCEST MRI is a technique for measuring extracellular pH (pHe) in the tumor microenvironment.
• Conventional CEST MRI requires high concentrations of small-molecule agents, limiting its clinical applicability.
• There is a need for more sensitive CEST agents to improve tumor pH imaging.

Purpose of the Study:

• To develop and evaluate nanoscale CEST agents for improved pH measurement in cancer.
• To compare the performance of a novel polymer nanoscale agent against a monomer agent and a conventional agent (iopamidol).
• To assess the feasibility of using these agents for *in vivo* acidoCEST MRI studies.

Main Methods:

• Synthesis and characterization of nanoscale polymer and monomer CEST agents.
• Optimization of CEST experimental conditions for pH measurements.
• Comparative *in vivo* acidoCEST MRI studies in a xenograft MDA-MB-231 mammary carcinoma mouse model.

Main Results:

• The polymer agent enabled acidoCEST MRI at 125-fold and 488-fold lower concentrations than the monomer agent and iopamidol, respectively.
• Both novel agents demonstrated negligible temperature dependence but showed concentration-dependent pH measurements.
• *In vivo* studies revealed distinct tumor pHe values: 6.33 ± 0.12 (iopamidol), 6.70 ± 0.15 (monomer), and 6.85 ± 0.15 (polymer), attributed to agent concentration effects.

Conclusions:

• Nanoscale CEST agents show significant promise for improving the sensitivity and reducing the required concentration for pH imaging in cancer.
• The concentration dependence of these agents must be carefully considered for accurate *in vivo* pHe quantification.
• Further research is warranted to optimize nanoscale agent design and application in CEST MRI.