A sensitive PARACEST contrast agent for temperature MRI: Eu ³⁺-DOTAM-glycine (Gly)-phenylalanine (Phe)

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 (Eu³⁺) 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 ∼75% greater for Eu³⁺-DOTAM-Gly-Phe compared to Eu³⁺-DOTAM-Gly at physiologic temperature (38°C) and pH (7.0 pH units) when using power level sufficiently low for in vivo imaging. Unlike Eu³⁺-DOTAM-Gly, whose CEST effect decreased with increasing temperature in the physiologic range, the CEST effect of Eu³⁺-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/°C), which was insensitive to pH and agent concentration. Temperature maps with SDs < 1°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 Eu³⁺-DOTAM-Gly-Phe; and 3) phantom C, mouse brain tissue with 4 mM Eu³⁺-DOTAM-Gly-Phe. The temperature sensitivity combined with the high CEST effect observed at low concentration using low saturation power (B₁) suggests this compound may be a good choice for in vivo temperature mapping at 9.4T.