Automated production of a sphingosine-1 phosphate receptor 1 (S1P1) PET radiopharmaceutical [11C]CS1P1 for human use

Luo, Zonghua; Gu, Jiwei; Dennett, Robert C.; Gaehle, Gregory; Perlmutter, Joel S.; Chen, Delphine L.; Benzinger, Tammie L.S.

doi:10.1016/j.apradiso.2019.06.029

Cited by 8 publications

(12 citation statements)

References 17 publications

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“…These results have important implications for the future schizophrenia subtype-based studies with in vivo PET S1PR1. The S1PR1 has recently emerged as a promising radiotracer for in vivo PET imaging (Liu et al, 2017; Liu et al, 2016; Liu et al, 2020; Luo et al, 2019). The S1PR1 protein upregulation only in Type 2 demonstrated in this study was in line with previous reports on the S1PR1 mRNA upregulation only in Type 2 schizophrenia patients (Bowen et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…A serious limitation of mRNA expression studies like that of Bowen et al (Bowen et al, 2019) is that they require brain tissue which is generally not available except at autopsy. Fortunately PET ligands for one of the genes differentially expressed in the Type 2 schizophrenic brains, sphingosine-1-phosphate receptor-1 (S1PR1) have been developed in the Mallinckrodt Institute of Radiology, Washington University in St. Louis (Jin et al, 2017; Liu et al, 2017; Liu et al, 2016; Liu et al, 2020; Luo et al, 2019). The present study examines the differential expression of S1PR1 in the DLPFC of Type 1 and Type 2 schizophrenic patients at the protein level as a preliminary step towards the use of PET to distinguish Type 1 from Type 2 schizophrenia during life.…”

Section: Introductionmentioning

confidence: 99%

“…S1PR1 radioligand has gained significant interest for in vivo targeted imaging of inflammation in brain diseases, with the recent FDA approval of the first orally administered S1PR1 receptor-targeted drug, FTY720 (Fingolimod) for multiple sclerosis (Marciniak et al, 2020). PET S1PR1 has recently gone into living humans successfully at Washington University in St. Louis (Liu et al, 2017; Liu et al, 2016; Liu et al, 2020; Luo et al, 2019). We have completed more than 7 PET S1PR1 studies in normal humans safely (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

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Differential sphingosine-1-phosphate receptor-1 protein expression in the dorsolateral prefrontal cortex between schizophrenia Type 1 and Type 2

Jiang

Brier³

et al. 2021

Preprint

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There is growing evidence that there are subtypes of schizophrenia (Bowen et al., 2019; Chand et al., 2020). Specifically, messenger ribonucleic acid (mRNA) gene expression findings on postmortem dorsolateral prefrontal cortex (DLPFC) suggest that schizophrenia patients can be divided into two groups, those with a relatively normal DLPFC transcriptome (Type 1) and those with hundreds of differentially expressed genes (Type 2). The clinical relevance of that finding is limited by the fact that autopsy tissue is required to distinguish Type 1 from Type 2 patients, however the PET target sphingosine-1-phosphate receptor-1 (S1PR1) is among the genes whose mRNA expression is upregulated in Type 2 compared to Type 1 patients (Bowen et al., 2019). As a preliminary study to validate this PET target, S1PR1 protein expression was assessed by receptor autoradiography and immunohistochemistry in the DLPFC from schizophrenic patients classified as Type 1 or Type 2 based on their DLPFC transcriptomes and from controls. S1PR1 protein expression is upregulated in Type 2 compared to Type 1 (p < 0.05) supporting the possibility that positron emission tomography (PET) can be used as a clinical test to distinguish these subgroups of schizophrenic patients during life.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential sphingosine-1-phosphate receptor-1 protein expression in the dorsolateral prefrontal cortex between schizophrenia Type 1 and Type 2

Jiang

Brier³

et al. 2021

Preprint

Self Cite

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“…CD69 has been found to suppress the activity of sphingosine-1 phosphate receptor 1 (S1P1), helping the TRM cells that remain in peripheral tissues [75]. The S1P1 receptor/gene, originally known as endothelial differentiation gene 1, acts by binding with a bioactive signaling molecule S1P1 [76]. It was suggested that CD69 expression might help retaining TRM cells in peripheral tissues by suppressing the activity of S1P1.…”

Section: Cd69mentioning

confidence: 99%

Resident Memory T Cells

Akbaba¹

2020

Cells of the Immune System

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Until recently, T cells were thought to remain in circulation until recruitment of the inflammation and only a small number of T cells remained in the peripheral tissues without inflammation. However, studies have found that a group of T cells settled in the tissues and remained there for a long time. Those cells are named as tissue-resident memory T cells (TRM). TRM cells are transcriptionally, phenotypically, and functionally distinct from other T cells, which recirculate between blood, secondary lymphoid organs, and non-lymphoid tissues. They undergo a distinct proliferation that discriminates them from circulating T cells and their main cell surface markers are CD69, CD103, and CD49a. Upon exposure to the same or similar diseases, TRM cells provide a first line of adaptive cellular defense against infection in peripheral non-lymphoid tissues, such as skin, lungs, digestive, and urogenital tracts. This approach forms the basis of a novel vaccination strategy called "prime and pull", which ensures long-term local immunity. On the other hand, abnormal activated and malignant TRM may contribute to numerous human inflammatory diseases such as psoriasis and vitiligo. Here in this chapter, we aimed to emphasize TRM cell location, migration, phenotypic structure, maintenance, and diseases associated with TRM cells.

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“…The pyrrole compound CS-0777 ( Figure 2 : [ 8 , 9 ]) provides also log P in an appropriate range for the blood–brain barrier passage (2.63). Although it is an agonist at the S1P1 and S1P3 subtypes of the sphingosine 1 phosphate receptor [ 54 , 55 , 56 , 57 ], the selectivity at S1P1 vs. S1P3 is approximately 10-fold that of fingolimod. Half maximal effective concentrations (EC 50 ) for agonist-induced binding of [ 35 S]GTPγ-S to human S1P1 and S1P3 receptors overexpressed in chinese hamster ovary (CHO) cells wereat 1.1 and 1.8 nM (S1P1) as well as at 200 nM and 350 nM (S1P3) in comparison to fingolimod (EC 50 : 0.29 and 0.37 nM, S1P1; EC 50 : 1.3 and 3.3 nM, S1P3) [ 57 ].…”

Section: Target Receptors and Ligandsmentioning

confidence: 99%

Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors

Pissarek

2020

Pharmaceutics

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Inflammatory processes preceding clinical manifestation of brain diseases are moving increasingly into the focus of positron emission tomographic (PET) investigations. A key role in inflammation and as a target of PET imaging efforts is attributed to microglia. Cerebellar microglia, with a predominant ameboid and activated subtype, is of special interest also regarding improved and changing knowledge on functional involvement of the cerebellum in mental activities in addition to its regulatory role in motor function. The present contribution considers small molecule ligands as potential PET tools for the visualization of several receptors recognized to be overexpressed in microglia and which can potentially serve as indicators of inflammatory processes in the cerebellum. The sphingosine 1 phosphate receptor 1 (S1P1), neuropeptide Y receptor 2 (NPY2) and purinoceptor Y12 (P2Y12) cannabinoid receptors and the chemokine receptor CX3CR1 as G-protein-coupled receptors and the ionotropic purinoceptor P2X7 provide structures with rather classical binding behavior, while the immune receptor for advanced glycation end products (RAGE) and triggering receptor expressed on the triggering receptor expressed on myeloid cells 2 (TREM2) might depend for instance on further accessory proteins. Improvement in differentiation between microglial functional subtypes in comparison to the presently used 18 kDa translocator protein ligands as well as of the knowledge on the role of polymorphisms are special challenges in such developments.

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Automated production of a sphingosine-1 phosphate receptor 1 (S1P1) PET radiopharmaceutical [11C]CS1P1 for human use

Cited by 8 publications

References 17 publications

Differential sphingosine-1-phosphate receptor-1 protein expression in the dorsolateral prefrontal cortex between schizophrenia Type 1 and Type 2

Differential sphingosine-1-phosphate receptor-1 protein expression in the dorsolateral prefrontal cortex between schizophrenia Type 1 and Type 2

Resident Memory T Cells

Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors

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