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.