Peptide-Based pH-Responsive MRI-CEST Agents: In Vivo Comparison between a Selected Pentapeptide and the Established Iopamidol Reference in Tumor pH Mapping Ability

Magnetic resonance imaging based on chemical exchange saturation transfer (MRI-CEST) has emerged as a powerful imaging technique for mapping physiological parameters, such as tissue pH, with high spatial resolution. This study explores the pH-responsive performance of a novel peptide-based CEST agent, selected among several candidates, when compared with the established contrast agent iopamidol. The selected hLys containing pentapeptide showed enhanced sensitivity and biocompatibility while maintaining an excellent CEST response. In vivo MRI studies further assessed its applicability for tumor pH imaging. The results demonstrate that the selected peptide-based agent displays good CEST contrast variations in response to pH changes, highlighting its potential as a pH-responsive CEST agent. The assessed pH values were very similar to those obtained upon the administration of iopamidol, a well-established pH-CEST agent. Notably, this result was obtained by administering a mass dose of contrast agent that is about 8-fold less than that used in the case of iopamidol. These findings pave the way for the development of peptide-derived MRI probes for noninvasive tumor microenvironment assessment.