title: A sensitive PARACEST contrast agent for temperature MRI: Eu3+-DOTAM-glycine (Gly)-phenylalanine (Phe).
abstract: Tissue temperature is a fundamental physiological parameter that can provide insight into pathological processes. The purpose of this study was to develop and characterize a novel paramagnetic chemical exchange saturation transfer (CEST) agent suitable for in vivo temperature mapping at 9.4T. The CEST properties of the europium (Eu(3+)) complex of the DOTAM-Glycine (Gly)-Phenylalanine (Phe) ligand were studied in vitro at 9.4T as a function of temperature, pH, and agent concentration. The transfer of magnetization (CEST effect) from the bound water to bulk water pools was approximately 75% greater for Eu(3+)-DOTAM-Gly-Phe compared to Eu(3+)-DOTAM-Gly at physiologic temperature (38 degrees C) and pH (7.0 pH units) when using power level sufficiently low for in vivo imaging. Unlike Eu(3+)-DOTAM-Gly, whose CEST effect decreased with increasing temperature in the physiologic range, the CEST effect of Eu(3+)-DOTAM-Gly-Phe was optimal at body temperature. A strong linear dependence of the chemical shift of the bound water pool on temperature was observed (0.3 ppm/ degrees C), which was insensitive to pH and agent concentration. Temperature maps with SDs < 1 degrees C were acquired at 9.4T in phantoms containing: 1) phantom A, an aqueous solution of 10 mM Eu(3+)-DOTAM-Gly-Phe; 2) phantom B, 5% bovine serum albumin (BSA) with 15 mM Eu(3+)-DOTAM-Gly-Phe; and 3) phantom C, mouse brain tissue with 4 mM Eu(3+)-DOTAM-Gly-Phe. The temperature sensitivity combined with the high CEST effect observed at low concentration using low saturation power (B(1)) suggests this compound may be a good choice for in vivo temperature mapping at 9.4T.
authors.affiliation: Center for Functional and Metabolic Mapping, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada.
authors.forename: Alex X
authors.initials: AX
authors.lastname: Li
authors.forename: Filip
authors.initials: F
authors.lastname: Wojciechowski
authors.forename: Mojmir
authors.initials: M
authors.lastname: Suchy
authors.forename: Craig K
authors.initials: CK
authors.lastname: Jones
authors.forename: Robert H E
authors.initials: RH
authors.lastname: Hudson
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Menon
authors.forename: Robert
authors.initials: R
authors.lastname: Bartha
mesh_terms: D000081:Acetamides / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D005063:Europium / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D015394:Molecular Structure; D019047:Phantoms, Imaging; D010649:Phenylalanine / Q000737:chemistry; D013696:Temperature
chemical_list: C522450:1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane; D000081:Acetamides; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D005063:Europium; D010649:Phenylalanine; D005998:Glycine