Accurate mapping of small changes in pH is essential to the diagnosis of diseases such as cancer. The difficulty in mapping pH accurately in vivo resides in the need for the probe to have a ratiometric response so as to be able to independently determine the concentration of the probe in the body independently from its response to pH. The complex FeII-DOTAm-F12 behaves as an MRI contrast agent with dual 19F and CEST modality. The magnitude of its CEST response is dependent both on the concentration of the complex and on the pH, with a significant increase in saturation transfer between pH 6.9 and 7.4, a pH range that is relevant to cancer diagnosis. The signal-to-noise ratio of the 19F signal of the probe, on the other hand, depends only on the concentration of the contrast agent and is independent of pH. As a result, the complex can ratiometrically map pH and accurately distinguish between pH 6.9 and 7.4. Moreover, the iron(II) complex is stable in air at room temperature and adopts a rare 8-coordinate geometry.
Bibliographical noteFunding Information:
This work was supported by the National Science Foundation Grant CAREER 1151665 (V.C.P.), by the NIH Clinical and Translational Science Award at the University of Minnesota (8UL1TR000114), and by the European H2020 IDentIFY grant (S.A.). G.F. was supported by an FIRC (Fondazione Italiana per la Ricerca sul Cancro AIRC) fellowship. The authors thank Dr. Sylvie Pailloux for her help with the manuscript preparation.