A Class of FeIII Macrocyclic Complexes with Alcohol Donor Groups as Effective T1 MRI Contrast Agents

Early studies suggested that Fe-III complexes cannot compete with Gd-III complexes as T-1 MRI contrast agents. Now it is shown that one member of a class of high-spin macrocyclic Fe-III complexes produces more intense contrast in mice kidneys and liver at 30 minutes post-injection than does a commercially used Gd-III agent and also produces similar T-1 relaxivity in serum phantoms at 4.7 T and 37 degrees C. Comparison of four different Fe-III macrocyclic complexes elucidates the factors that contribute to relaxivity in vivo including solution speciation. Variable-temperature O-17 NMR studies suggest that none of the complexes has a single, integral inner-sphere water that exchanges rapidly on the NMR timescale. MRI studies in mice show large in vivo differences of three of the Fe-III complexes that correspond, in part, to their r(1) relaxivity in phantoms. Changes in overall charge of the complex modulate contrast enhancement, especially of the kidneys.