Work

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Year: 2019

Type: article

Abstract: Purpose CEST has become a preeminent technology for the rapid detection and grading of tumors, securing its widespread use in both laboratory and clinical research. However, many existing CEST MRI agents exhibit a sensitivity limitation due to small chemical shifts between their exchangeable protons and water. We propose a new group of CEST MRI agents, free‐base porphyrins and chlorin, with large exchangeable proton chemical shifts from water for enhanced detection. Methods To test these newly identified CEST agents, we acquired a series of Z‐spectra at multiple pH values and saturation field strengths to determine their CEST properties. The data were analyzed using the quantifying exchange using saturation power method to quantify exchange rates. After identifying several promising candidates, a porphyrin solution was injected into tumor‐bearing mice, and MR images were acquired to assess detection feasibility in vivo. Results Based on the Z‐spectra, the inner nitrogen protons in free‐base porphyrins and chlorin resonate from −8 to −13.5 ppm from water, far shifted from the majority of endogenous metabolites (0‐4 ppm) and Nuclear Overhauser enhancements (−1 to −3.5 ppm) and far removed from the salicylates, imidazoles, and anthranillates (5‐12 ppm). The exchange rates are sufficiently slow to intermediate (500‐9000 s−1) to allow robust detection and were sensitive to substituents on the porphyrin ring. Conclusion These results highlight the capabilities of free‐base porphyrins and chlorin as highly upfield CEST MRI agents and provide a new scaffold that can be integrated into a variety of diagnostic or theranostic agents for biomedical applications.

Source: Magnetic Resonance in Medicine

DOI: 10.1002/mrm.27753