Towards an Improved Design of MRI Contrast Agents: Synthesis and Relaxometric Characterisation of Gd-HPDO3A Analogues |
| |
Authors: | Dr. Louise R. Tear Dr. Carla Carrera Dr. Eliana Gianolio Prof. Silvio Aime |
| |
Affiliation: | 1. Department of Molecular Biotechnology and Health Sciences, Molecular Imaging Centre, University of Torino, Via Nizza 52, 10126 Torino, Italy;2. Institute of Biostructures and Bioimaging, National Research Council, Via Nizza 52, 10126 Torino, Italy |
| |
Abstract: | The properties of LnIII-HPDO3A complexes as relaxation enhancers and paraCEST agents are essentially related to the hydroxylpropyl moiety. A series of three HPDO3A derivatives, with small modifications to the hydroxyl arm, were herein investigated to understand how heightened control can be gained over the parameters involved in the design of these agents. A full 1H and 17O-NMR relaxometric analysis was conducted and demonstrated that increasing the length of the OH group from the lanthanide centre significantly enhanced the water exchange rate of the gadolinium complex, but with a subsequent reduction in kinetic stability. Alternatively, the introduction of an additional methyl group, which increased the steric bulk around the OH moiety, resulted in the formation of almost exclusively the TSAP isomer (95 %) as identified by 1H-NMR of the europium complex. The gadolinium analogue of this complex also exhibited a very fast water exchange rate, but with no detectable loss of kinetic stability. This complex therefore demonstrates a notable improvement over Gd-HPDO3A. |
| |
Keywords: | gadolinium lanthanides macrocycles MRI contrast agents relaxometry |
|
|