| The ability to determine pH in vivo using magnetic resonance imaging (MRI) would be a major advance in diagnostic medicine of tumors. Contrast agents are widely used in MRI and a number of contrast agents capable of reporting changes in pH have been proposed. One of the major obstacles in imaging absolute pH by MRI is that the concentration of the pH-sensitive contrast agent must be known. This study aims to develop a single injectable solution that will enable monitoring of pH changes by the addition of a concentration marker component to yield an image map of extracellular pH of tissue in a single imaging study. This strategy takes advantage of the ideal pH reporting characteristics of GdNP-DO3A, a pH sensitive agent that shortens the T1 of tissue water and thereby changes image intensity in T1-weighted images. To overcome the problem of potential uneven tissue distribution of the pH sensitive agent, analogous dysprosium complexes that are insensitive to changes in pH were synthesized. DyHB-DO3A and DyNMB-DO3A were envisioned to be used as T2 shortening agents and hence a concentration marker. Thus, by combining a pH responsive GdNP-DO3A with the non-pH responsive dysprosium complex, a quantitative map of tissue pH will be generated after a single injection of drug. |
