| Affiliation: | 1. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA;2. CMUC, Department of Mathematics, University of Coimbra, Coimbra, Portugal;3. Department of Life Sciences and Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal CIBIT- Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal |
| Abstract: | Paramagnetic chemical exchange saturation transfer (paraCEST) agents are well-suited for imaging tissue pH because the basis of CEST, chemical exchange, is inherently sensitive to pH. Several previous pH-sensitive paraCEST agents were based on an exchanging Ln3+-bound water molecule as the CEST antenna but this design often added additional line-broadening to the bulk water signal due to T2 exchange. We report herein a pH-sensitive paraCEST agent that lacks an inner-sphere water molecule but contains one Ln-bound −OH group for CEST activation. The Yb3+ complex, Yb( 1 ), displayed a single, highly shifted CEST peak originating from the exchangeable Yb-OH proton, the frequency of which changed over the biologically relevant pH range. CEST images of phantoms ranging in pH from 6 to 8 demonstrate the potential of this agent for imaging pH. Initial rodent imaging studies showed that Gd( 1 ) remains in the vascular system much longer than anticipated but is cleared slowly via renal filtration. |
