Abstract
Objective19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F 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. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T.Results19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe.ConclusionDOTP-based 19F 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.
Highlights
Magnetic resonance imaging (MRI) is a technique commonly used for clinical and preclinical imaging
The solution was vacuum dried, and the solid residue was redissolved in water to prepare a 20 mM stock solution of the complex, which was appropriately diluted for the following relaxation and MRI measurements
Diamagnetic La3+ has small effect on T1 relaxation time, but a stronger effect on T2 relaxation time
Summary
Magnetic resonance imaging (MRI) is a technique commonly used for clinical and preclinical imaging. Magnetic resonance may detect all the isotopes with an odd number of protons and/or neutrons. Other nuclei present in the living systems, such as 31P, 13C, and 23Na, among others, are interesting targets for imaging or spectroscopic techniques [1]. Amount of fluorine (19F) in living organisms is negligible, 19F MRI is a potentially interesting tool for preclinical or even clinical imaging [2, 3], as long as a suitable fluorinated tracer is used as a contrast agent. 19F nucleus has a resonance frequency close to the proton frequency. Standard commercial scanners can be used for fluorine detection after introducing only minor hardware and software changes
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