title: Spectral properties of a bifunctional PARACEST europium chelate: an intermediate for targeted imaging applications.
abstract: This report describes a preliminary study to investigate the effect of structural variations in a bifunctional ligand being developed for targeted PARACEST applications. Utilizing Eu-DOTA-4AmCE as the functional PARACEST core, a nitro-aromatic functionality was incorporated to provide the point for conjugation. This intermediate possesses a coordinated water proton signal at 57 ppm which upon saturation produces a 22% decrease in bulk water signal intensity using 10 mM agent. Curve fitting analysis of the CEST spectrum to an exchange model based upon modified Bloch equations gave an estimate of 687 +/- 100 micros for the bound water lifetime (tau(m)). Although substantially longer than the 382 micros observed for the parent chelate structure, this water exchange rate remains in the necessary window to produce a significant CEST effect. These findings demonstrate the need to recognize the influence of bifunctional linkers on water exchange rates in lanthanide complexes of this type and the potential for using this functionality as a means of fine-tuning PARACEST performance.
authors.affiliation: Macrocyclics, 2110 Research Row, STE 425, Dallas, TX 75235, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Adair
authors.forename: Mark
authors.initials: M
authors.lastname: Woods
authors.forename: Piyu
authors.initials: P
authors.lastname: Zhao
authors.forename: Azhar
authors.initials: A
authors.lastname: Pasha
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Winter
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.forename: Phillip
authors.initials: P
authors.lastname: Athey
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.forename: Garry E
authors.initials: GE
authors.lastname: Kiefer
mesh_terms: D002614:Chelating Agents / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry*; D013057:Spectrum Analysis
chemical_list: D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; C475854:europium(III) chelate-2,2',2'',2'''-((4-((4-isothiocyanatophenyl)ethynyl)pyridine-2,6-diyl)bis(methylenenitrilo))tetrakis(acetic acid)