Low-Molecular-Weight Paramagnetic F-19 Contrast Agents For Fluorine Magnetic Resonance Imaging

Objective(19)F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable F-19 relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested.MethodsComplexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. F-19 relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo F-19 MRI was performed at 4.7T.Results(19)F relaxation times strongly depended on the chelated lanthanide(III) ion. T-1 ranged from 6.5 to 287ms, T-2 from 3.9 to 124.4ms, and T-2* from 1.1 to 3.1ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; F-19 MRI in vivo confirmed the in vivo applicability of the probe.ConclusionDOTP-based F-19 probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.