A Frequency‐Selective pH‐Responsive paraCEST Agent

Abstract

Paramagnetic chemical exchange saturation transfer (paraCEST) agents are well-suited for imaging tissue pH because the basis of CEST,c hemical exchange,i si nherently 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.W er eport herein ap H-sensitive paraCEST agent that lacks an inner-sphere water molecule but contains one Lnbound ÀOH group for CEST activation. The Yb 3+ complex, Yb(1), displayed as ingle,h ighly 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 6to8demonstrate 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.

Lanthanide complexes with polyaminopolycarboxylates as prospective NMR/MRI diagnostic probes: peculiarities of molecular structure, dynamics and paramagnetic properties

“…It is interesting in studying the interrelationships between the structure, paramagnetic properties, and the molecular dynamics of Ln-DOTA complexes and DOTA-like ligands [60,109,110,[112][113][114][115][116][117][118][119][120]. The example of first type about intramolecular dynamics in DOTA and DOTA complexes with La 3+ , Eu 3+ , Yb 3+ and Lu 3+ have been reported based on using 2D EXSY NMR techniques and determining the coalescence temperature [119].…”

Hypoxia-Responsive Luminescent CEST MRI Agent for In Vitro and In Vivo Tumor Detection and Imaging

“…In addition, para-CEST MRI contrast agents have been used to detect caspase-3, an important apoptosis biomarker . pH-responsive para-CEST agents have also been reported for detecting changes in kidney pH levels . Other pH-sensitive − and Zn­(II)-responsive CEST MRI probes are known .…”

“…34 pH-responsive para-CEST agents have also been reported for detecting changes in kidney pH levels. 35 Other pH-sensitive 36−38 and Zn(II)-responsive CEST MRI probes are known. 39 However, to the best of our knowledge, hypoxia-responsive CEST probes have yet to be described.…”

Methylated tetra‐amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST

“…Similarly, other work with Tm 3+ and Eu 3+ salts of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetate tetraglycinate (DOTA‐(gly) 4 4‐ ) show that both TmDOTA‐(gly) 4 − and EuDOTA‐(gly) 4 − possess BIRDS and CEST properties 15,28 . Some novel work with Yb 3+ complexes of a slightly modified DOTP 8− chelate (i.e., 1,4,7‐tris (methylenephosphonic acid)‐10‐(2‐hydroxypropyl)‐1,4,7,10‐tetraazacyclododecane) develops unique pH sensitive CEST properties 29 . Moreover, for EuDOTA‐(gly) 4 − , changing the oxidation state from +3 (when it is BIRDS/CEST active) to +2 enables this probe to generate both T 1 sensitivity and photoacoustic imaging 30 …”

“…(methylenephosphonic acid)-10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane) develops unique pH sensitive CEST properties 29. Moreover, for EuDOTA-(gly) 4 À…”