Fluorinated substrates are widely applied as pharmaceuticals. Even their potential as contrast agents has already been demonstrated.¹ Due to the importance of these different application fields, studies concerning metabolization, the interaction with other substrates or their site of action become increasingly interesting. MR techniques qualify for the detection of fluorinated molecules but the applicable concentrations in vivo are, in many cases, too low to be detected within a reasonable timeframe. This problem can be solved by the application of hyperpolarization methods such as Chemical Induced Dynamic Nuclear Polarization (CIDNP)² and photo-CIDNP³. Aside from ¹H and ¹³C, even the MR signals of ¹⁹F nuclei can be enhanced. In 2013 and 2015 Feldmeier et al. showed, ^4,5 that signal enhancements for ¹H nuclei can be generated using a simple LED based setup. Their experiments were based on the photo-CIDNP effect which is usually generated by a laser induced reversible photochemical reaction of excited photosensitizers and aromatic systems. It was demonstrated, that the CIDNP effect can be achieved for flavin derivatives using CD₃CN or CD₃CN/D₂O-mixtures (1:1) as solvents. Nevertheless, for an in vivo application the use of physiologically compatible solvents is necessary. Here we present experiments using an analogous assembly for the generation of enhanced ¹⁹F NMR signals of 3-fluoro-DL-tyrosine in pure D₂O. Furthermore, the influence of β-cyclodextrin (β-CD) as a host molecule (host-guest complex: β-CD-tyrosine) was studied.

In the first experiment 0.4 mg of 3-fluoro-DL-tyrosine (ABCR) and 0.5 mg of riboflavin 5′-monophosphate sodium salt hydrate (Sigma) were dissolved in 600 µl D₂O (Deutero GmbH) in a 5 mm NMR-tube. An optical fibre, connected to a Cree XP-E high power LED (455 nm), was centrally positioned in the solution. The LED-device (3.2V, ~350mA) was controlled by a pulse programme of a 7T NMR spectrometer (Bruker WB-300 ultrashield). Irradiation times between 0.5 s and 15 s were chosen.

In a further study different concentrations of β-CD (Sigma) were added to examine the influence of the formation of a host-guest complex. ¹⁹F NMR spectra were detected using a 90°-pulse (¹⁹F: P1 = 32.5 µs, PL1 = 17 W).

A third measurement series was performed using the same concentration of the non-fluorinated L-tyrosine for comparison of proton spectra derived from LED induced CIDNP.

Subsequently after irradiation a clear ¹⁹F signal enhancement could be observed for the chosen system. Fig. 2 exemplarily shows the comparison between a ¹⁹F spectrum which was detected without LED irradiation (blue) and a spectrum after 6s of irradiation (red). For this experiment an enhancement factor of 3 could be calculated.

The measurement series with different durations of irradiation between 0.5s and 15s shows that a maximum of signal enhancement is reached at 6s. The addition of β-CD led to a change of the chemical shift that can be observed for the ¹⁹F NMR signal indicating the formation of a host-guest complex.⁶ Furthermore, it could be shown that even for this complex a ¹⁹F NMR signal enhancement can be generated by the application of the LED-device.

In contrast to the ¹⁹F substituted derivative, where no significant change in ¹H NMR spectra could be detected, the proton spectra of the L-tyrosine analogue show clear antiphase signals.

¹⁹F tyrosine was already investigated by Kuprov et al. using an argon laser.⁷ Within this experiment a signal enhancement of 20 was detected after 7s of irradiation. The high laser power led to a significant warming of the sample. Hence, this approach is not suitable for a direct application in biological systems.

In this novel study showing hyperpolarization of a ¹⁹F nucleus using simple LED-irradiation rather no warming could be detected.

Despite of a quite low signal enhancement this study illustrates the potential of this promising new method. Working with an LED setup opens up a new strategy for in vivo applications and might allow for the performance of a CIDNP experiment direct at the location of interest within a living organism.