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A Frequency‐Selective pH‐Responsive paraCEST Agent
Author(s) -
Ratnakar S. James,
Chirayil Sara,
Funk Alexander M.,
Zhang Shanrong,
Queiró João F.,
Geraldes Carlos F. G. C.,
Kovacs Zoltan,
Sherry A. Dean
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008888
Subject(s) - chemistry , molecule , proton , paramagnetism , small molecule , nuclear magnetic resonance , organic chemistry , biochemistry , physics , quantum mechanics
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 Ln 3+ ‐bound water molecule as the CEST antenna but this design often added additional line‐broadening to the bulk water signal due to T 2 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 Yb 3+ 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.