¹⁹F‐lanthanide complexes with increased sensitivity for ¹⁹F‐MRI: Optimization of the MR acquisition

Abstract

Fluorine-19 magnetic resonance methods offer advantages for molecular or cellular imaging in vivo due to the absence of radioactivity, lack of naturally occurring background signal, and the ability to easily combine measurements with anatomical MRI. Previous studies have shown that 19 F-MRI sensitivity is limited to millimolar concentrations by slow longitudinal relaxation. In this study, a new class of macrocyclic fluorinated lanthanide complexes is investigated where relaxation rates are significantly shortened by proximity of the fluorine group to a paramagnetic lanthanide ion located within the same molecule. Longitudinal and transverse relaxation rates are field dependent and in the range 50-150 s 21 and 70-200 s 21 , respectively, at 7 T. Relaxation rates in these complexes are a function of the molecular structure and are independent of concentration at biologically relevant levels, so can be used as criteria to optimize imaging acquisition. Phantom experiments at 7 T indicate a lower limit for detection by imaging of 20 mM. Magn Reson Med 66:931-936,

Enhancing magnetic resonance imaging with contrast agents for ultra-high field strengths

“…6) were reported by Blamire and co-workers. 63 They used phosphonate-based 1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (DO3A)-type ligands that were metalated with different lanthanide ions. Selection of the lanthanide ion and the imaging parameters were found to be key factors for using these agents for ultra-high field applications.…”

A new paramagnetically shifted imaging probe for MRI

“…Relaxation rates are a key factor in defining detection sensitivity. By manipulating the intramolecular distances from the lanthanide ion to the reporter group, the R 1 relaxation rate can be increased, allowing the MR sequence to be run rapidly and with high flip angle, maximizing the signal collection per unit time . R 1 for the [Dy.L 1 ] − probe was 128s −1 at 7 T, rising to 160 s −1 at 9.4 T and 185 s −1 at 11.7 T, which is slightly lower than the relaxation rate of the H‐3 protons in [TmDOTMA] (reported to be 188 s −1 at 9.4 T and 211 s −1 at 11.7 T) and substantially lower than for the H‐6 protons of TmDOTP (reported as 625 s −1 at 11.7 T) .…”

“…For simple detection of the agent in vivo, an optimized 3D gradient‐echo (3DGE) sequence was employed. Our previous work has shown that once an imaging spectral width (SW) is defined (which, with the choice of imaging matrix size determines the minimum TE), the scan should be collected at the shortest available TR under Ernst angle conditions . The minimum allowed SW for these experiments is defined by the fat‐PARASHIFT frequency difference.…”

New frontiers and developing applications in 19F NMR

“…This is quite analogous to optical FRET (Förster (fluorescence) resonance energy transfer), where proximity controls signal. Molecular structures are crucial to generate optimal proximity relevant to a particular lanthanide [113, 161–163]. The proximity may be altered by molecular cleavage revealing enzyme activity as discussed in Section 4 [164–166].…”