<i>In vivo</i> detection of teriflunomide-derived fluorine signal during neuroinflammation using fluorine MR spectroscopy

Prinz, Christian; Starke, Ludger; Millward, Jason M.; Fillmer, Ariane; Delgado, Paula Ramos; Waiczies, Helmar; Pohlmann, Andreas; Rothe, Michael; Nazaré, Marc; Paul, Friedemann; Niendorf, Thoralf; Waiczies, Sonia

doi:10.7150/thno.47130

Cited by 11 publications

(82 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This variation in the SNR gain could reflect variations in pH in the stomach that could affect relaxation times of TF. 16 Future comparative studies are needed to focus on organ systems more relevant to the pathophysiology of MS such as the CNS.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Pentafluorosulfanyl (SF₅) as a Superior ¹⁹F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

“…SNR was a major limitation in our previous study due to the low TF availability in vivo, thereby prohibiting imaging or localized MRS to specify its location in vivo. 16 …”

mentioning

confidence: 99%

Pentafluorosulfanyl (SF₅) as a Superior ¹⁹F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous individual factors underlie the discrepant CSF and plasma concentrations of drugs. One possibility could be fluorinated drugs, with the detection of fluorine signals using MR spectroscopy [154].…”

Section: Chronic Ms Dmts With Central Effect Beyond the Bbbmentioning

confidence: 99%

Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment

Bălaşa

Barcutean

Mosora

et al. 2021

IJMS

View full text Add to dashboard Cite

The disruption of blood–brain barrier (BBB) for multiple sclerosis (MS) pathogenesis has a double effect: early on during the onset of the immune attack and later for the CNS self-sustained ‘inside-out’ demyelination and neurodegeneration processes. This review presents the characteristics of BBB malfunction in MS but mostly highlights current developments regarding the impairment of the neurovascular unit (NVU) and the metabolic and mitochondrial dysfunctions of the BBB’s endothelial cells. The hypoxic hypothesis is largely studied and agreed upon recently in the pathologic processes in MS. Hypoxia in MS might be produced per se by the NVU malfunction or secondary to mitochondria dysfunction. We present three different but related terms that denominate the ongoing neurodegenerative process in progressive forms of MS that are indirectly related to BBB disruption: progression independent of relapses, no evidence of disease activity and smoldering demyelination or silent progression. Dimethyl fumarate (DMF), modulators of S1P receptor, cladribine and laquinimode are DMTs that are able to cross the BBB and exhibit beneficial direct effects in the CNS with very different mechanisms of action, providing hope that a combined therapy might be effective in treating MS. Detailed mechanisms of action of these DMTs are described and also illustrated in dedicated images. With increasing knowledge about the involvement of BBB in MS pathology, BBB might become a therapeutic target in MS not only to make it impenetrable against activated immune cells but also to allow molecules that have a neuroprotective effect in reaching the cell target inside the CNS.

show abstract

“…However, other nuclei with nonzero spin, e.g., 19 F, can also be used in MR experiments [13,14]. For investigations concerning drugs biodistribution and accumulation, magnetic resonance imaging and spectroscopy on 19 F nuclei have brought much interest [15][16][17]. There are several properties of 19 F nucleus that make it an excellent tracer for in vivo imaging of exogenous substances.…”

Section: Introductionmentioning

confidence: 99%

Polyaminoacid Based Core@shell Nanocarriers of 5-Fluorouracil: Synthesis, Properties and Theranostics Application

Szczęch

Hinz

Łopuszyńska

et al. 2021

IJMS

View full text Add to dashboard Cite

Cancer is one of the most important health problems of our population, and one of the common anticancer treatments is chemotherapy. The disadvantages of chemotherapy are related to the drug’s toxic effects, which act on cancer cells and the healthy part of the body. The solution of the problem is drug encapsulation and drug targeting. The present study aimed to develop a novel method of preparing multifunctional 5-Fluorouracil (5-FU) nanocarriers and their in vitro characterization. 5-FU polyaminoacid-based core@shell nanocarriers were formed by encapsulation drug-loaded nanocores with polyaminoacids multilayer shell via layer-by-layer method. The size of prepared nanocarriers ranged between 80–200 nm. Biocompatibility of our nanocarriers as well as activity of the encapsulated drug were confirmed by MTT tests. Moreover, the ability to the real-time observation of developed nanocarriers and drug accumulation inside the target was confirmed by fluorine magnetic resonance imaging (19F-MRI).

show abstract

In vivo detection of teriflunomide-derived fluorine signal during neuroinflammation using fluorine MR spectroscopy

Cited by 11 publications

References 98 publications

Pentafluorosulfanyl (SF₅) as a Superior ¹⁹F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives

Pentafluorosulfanyl (SF₅) as a Superior ¹⁹F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives

Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment

Polyaminoacid Based Core@shell Nanocarriers of 5-Fluorouracil: Synthesis, Properties and Theranostics Application

Contact Info

Product

Resources

About

In vivo detection of teriflunomide-derived fluorine signal during neuroinflammation using fluorine MR spectroscopy

Cited by 11 publications

References 98 publications

Pentafluorosulfanyl (SF5) as a Superior 19F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives

Pentafluorosulfanyl (SF5) as a Superior 19F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives

Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment

Polyaminoacid Based Core@shell Nanocarriers of 5-Fluorouracil: Synthesis, Properties and Theranostics Application

Contact Info

Product

Resources

About

Pentafluorosulfanyl (SF₅) as a Superior ¹⁹F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives

Pentafluorosulfanyl (SF₅) as a Superior ¹⁹F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives