New nonmetallic Imidazole MRI contrast agents for performing functional MRI of kidneys

S. Bo, K.D. Pavuluri, Y. Wu, N. Yadav, M. Pomper, F. Sedaghat, M. Kates, M.T. McMahon
Johns Hopkins University,
United States

Keywords: MRI contrast agents, diagnostic imaging

Summary:

Urinary tract obstructions (UTOs) are impairments in the flow of urine and can lead to pain, infection, and irreversible kidney damage if left undiagnosed and untreated. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism readily implemented on standard 3 T clinical scanners with one of its promising features sensitivity to environmental changes including changes in pH values. CEST MRI contrast can be produced by a number of organic compounds with exchangeable protons, such as glucose, creatine, nucleic acids and peptides2, however, most organic CEST agents suffer from reduced sensitivity because of their small exchangeable proton chemical shift (< 4.0 ppm). Previously our group has reported that the intramolecular hydrogen bond helps to shift the exchangeable protons to higher ppm (> 6.0 ppm). In this study, 14 new imidazole CEST agents were synthesized and tested for detecting renal impairment on a UTO mouse model. A number of our synthesized imidazole compounds provided significant pH sensitive contrast at ~7.5 ppm downfield from water. We selected one for testing and injected into UTO mice to perform functional MRI of the kidneys. Figure 1 shows the contrast build up with time. For these mice a CEST contrast of 25% was obtained in the healthy kidney at peak contrast while only 10% is observed in the obstructed kidney. In addition, some fine structure was apparent in the contrast images including differentiation between inner and outer medulla. CONCLUSION: We have developed a convenient synthesis for the I45DCs imidazole CEST agents. In vitro CEST contrast data of these compounds showed significant dependence on pH, which could be applied to produce pH maps. In vivo CEST MRI showed excellent delineation between unobstructed and obstructed kidneys on a UTO mouse model. This class of agent appears promising for clinical application.