Fluorine (
19
F) magnetic
resonance imaging (MRI) is severely
limited by a low signal-to noise ratio (SNR), and tapping it for
19
F drug detection in vivo still poses a significant challenge.
However, it bears the potential for label-free theranostic imaging.
Recently, we detected the fluorinated dihydroorotate dehydrogenase
(DHODH) inhibitor teriflunomide (TF) noninvasively in an animal model
of multiple sclerosis (MS) using
19
F MR spectroscopy (MRS).
In the present study, we probed distinct modifications to the CF
3
group of TF to improve its SNR. This revealed SF
5
as a superior alternative to the CF
3
group. The value
of the SF
5
bioisostere as a
19
F MRI reporter
group within a biological or pharmacological context is by far underexplored.
Here, we compared the biological and pharmacological activities of
different TF derivatives and their
19
F MR properties (chemical
shift and relaxation times). The
19
F MR SNR efficiency
of three MRI methods revealed that SF
5
-substituted TF has
the highest
19
F MR SNR efficiency in combination with an
ultrashort echo-time (UTE) MRI method. Chemical modifications did
not reduce pharmacological or biological activity as shown in the
in vitro dihydroorotate dehydrogenase enzyme and T cell proliferation
assays. Instead, SF
5
-substituted TF showed an improved
capacity to inhibit T cell proliferation, indicating better anti-inflammatory
activity and its suitability as a viable bioisostere in this context.
This study proposes SF
5
as a novel superior
19
F MR reporter group for the MS drug teriflunomide.
This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Siponimod is a fluorinated drug approved for treatment of secondary progressive multiple sclerosis. We detect 19F-MR signal in the liver, brain, kidneys, and thymus, and achieve the first 19F-MR images of a disease modifying drug, both in the liver and brain ex vivo and in a proof-of-concept in vivo experiment. Clear concentration differences between lobes of the liver or regions of the CNS can be observed. We have demonstrated the feasibility of using 19F-MRI to study the distribution of disease modifying drugs and improve our understanding of pharmacokinetics or guide therapeutic decisions.
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