In vivo imaging of neuroinflammation in the rodent brain with [11C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

2010 ◽  
Vol 38 (3) ◽  
pp. 509-514 ◽  
Author(s):  
Fabien Chauveau ◽  
Hervé Boutin ◽  
Nadja Van Camp ◽  
Cyrille Thominiaux ◽  
Philippe Hantraye ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Translocator Protein ◽  
Rodent Brain ◽  
Translocator Protein 18 Kda

scholarly journals Optimised GMP-compliant production of [18F]DPA-714 on the Trasis AllinOne module

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Klaudia A. Cybulska ◽  
Vera Bloemers ◽  
Lars R. Perk ◽  
Peter Laverman
Keyword(s):  
Significant Degree ◽  
Translocator Protein ◽  
Positron Emission ◽  
Leaving Group ◽  
Inflammatory Processes ◽  
Single Production ◽  
Translocator Protein 18 Kda ◽  
Radiochemical Yields ◽  
Specific Ligand

Abstract Background The translocator protein 18 kDa is recognised as an important biomarker for neuroinflammation due to its soaring expression in microglia. This process is common for various neurological disorders. DPA-714 is a potent TSPO-specific ligand which found its use in Positron Emission Tomography following substitution of fluorine-19 with fluorine-18, a positron-emitting radionuclide. [18F]DPA-714 enables visualisation of inflammatory processes in vivo non-invasively. Radiolabelling of this tracer is well described in literature, including validation for clinical use. Here, we report significant enhancements to the process which resulted in the design of a fully GMP-compliant robust synthesis of [18F]DPA-714 on a popular cassette-based system, Trasis AllinOne, boosting reliability, throughput, and introducing a significant degree of simplicity. Results [18F]DPA-714 was synthesised using the classic nucleophilic aliphatic substitution on a good leaving group, tosylate, with [18F]fluoride using tetraethylammonium bicarbonate in acetonitrile at 100∘C. The process was fully automated on a Trasis AllinOne synthesiser using an in-house designed cassette and sequence. With a relatively small precursor load of 4 mg, [18F]DPA-714 was obtained with consistently high radiochemical yields of 55-71% (n=6) and molar activities of 117-350 GBq/µmol at end of synthesis. With a single production batch, starting with 31-42 GBq of [18F]fluoride, between 13-20 GBq of the tracer can be produced, enabling multi-centre studies. Conclusion To the best of our knowledge, the process presented herein is the most efficient [18F]DPA-714 synthesis, with advantageous GMP compliance. The use of a Trasis AllinOne synthesiser increases reliability and allows rapid training of production staff.

scholarly journals Novel Pyrazolo[1,5-a]pyrimidines as Translocator Protein 18 kDa (TSPO) Ligands: Synthesis, in Vitro Biological Evaluation, [18F]-Labeling, and in Vivo Neuroinflammation PET Images

2015 ◽  
Vol 58 (18) ◽  
pp. 7449-7464 ◽  
Author(s):  
Annelaure Damont ◽  
Vincent Médran-Navarrete ◽  
Fanny Cacheux ◽  
Bertrand Kuhnast ◽  
Géraldine Pottier ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Translocator Protein ◽  
Translocator Protein 18 Kda

scholarly journals Voxel-Based Imaging of Translocator Protein 18Kda (TSPO) in High-Resolution PET

2013 ◽  
Vol 33 (3) ◽  
pp. 348-350 ◽  
Author(s):  
Ji Hyun Ko ◽  
Yuko Koshimori ◽  
Romina Mizrahi ◽  
Pablo Rusjan ◽  
Alan A Wilson ◽  
...  
Keyword(s):  
Relative Equilibrium ◽  
Compartment Model ◽  
Graphical Analysis ◽  
Translocator Protein ◽  
Proof Of Concept ◽  
Tissue Compartment ◽  
Potential Biomarker ◽  
Translocator Protein 18 Kda ◽  
Significant Attention

In vivo imaging of translocator protein 18 kDa (TSPO) has received significant attention as potential biomarker of microglia activation. Several radioligands have been designed with improved properties. Our group recently developed an 18F-labeled TSPO ligand, [18F]-FEPPA, and confirmed its reliability with a 2-tissue compartment model. Here, we extended, in a group of healthy subjects, its suitability for use in voxel-based analysis with the newly proposed graphical analysis approach, Relative-Equilibrium-Gjedde-Patlak (REGP) plot. The REGP plot successfully replicated the total distribution volumes estimated by the 2-tissue compartment model. We also showed its proof-of-concept in a patient with possible meningioma showing increased [18F]-FEPPA total distribution volume.

Unbinding of Translocator Protein 18 kDa (TSPO) Ligands: From in Vitro Residence Time to in Vivo Efficacy via in Silico Simulations

2019 ◽  
Vol 10 (8) ◽  
pp. 3805-3814 ◽  
Author(s):  
Agostino Bruno ◽  
Elisabetta Barresi ◽  
Nicola Simola ◽  
Eleonora Da Pozzo ◽  
Barbara Costa ◽  
...  
Keyword(s):  
Residence Time ◽  
In Silico ◽  
Translocator Protein ◽  
In Vivo Efficacy ◽  
Translocator Protein 18 Kda

scholarly journals In vivo Evaluation of Inflammatory Bowel Disease with the Aid of μPET and the Translocator Protein 18 kDa Radioligand [18F]DPA-714

2014 ◽  
Vol 17 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Nicholas Bernards ◽  
Géraldine Pottier ◽  
Benoit Thézé ◽  
Frédéric Dollé ◽  
Raphael Boisgard
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Translocator Protein ◽  
In Vivo Evaluation ◽  
Inflammatory Bowel ◽  
Translocator Protein 18 Kda

scholarly journals Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [18F]-FEPPA

2012 ◽  
Vol 32 (6) ◽  
pp. 968-972 ◽  
Author(s):  
Romina Mizrahi ◽  
Pablo M Rusjan ◽  
James Kennedy ◽  
Bruce Pollock ◽  
Benoit Mulsant ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Time Activity ◽  
Genetic Groups ◽  
Positron Emission ◽  
Translocator Protein 18 Kda ◽  
Human Brains ◽  
New Generation

[18F]-FEPPA binds to the 18-kDa translocator protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of the PET signal with new generation TSPO PET radioligands are confounded by large interindividual variability in binding affinity. This presents as a trimodal distribution, reflecting high-affinity binders (HABs), low-affinity binder (LAB), and mixed-affinity binders (MABs). Here, we show that one polymorphism (rs6971) located in exon 4 of the TSPO gene, which results in a nonconservative amino-acid substitution from alanine to threonine (Ala147Thr) in the TSPO protein, predicts [18F]-FEPPA total distribution volume in human brains. In addition, [18F]-FEPPA exhibits clearly different features in the shape of the time activity curves between genetic groups. Testing for the rs6971 polymorphism may allow quantitative interpretation of TSPO PET studies with new generation of TSPO PET radioligands.

scholarly journals Propofol Decreases In Vivo Binding of 11C-PBR28 to Translocator Protein (18 kDa) in the Human Brain

2012 ◽  
Vol 54 (1) ◽  
pp. 64-69 ◽  
Author(s):  
C. S. Hines ◽  
M. Fujita ◽  
S. S. Zoghbi ◽  
J. S. Kim ◽  
Z. Quezado ◽  
...  
Keyword(s):  
Human Brain ◽  
Translocator Protein ◽  
In Vivo Binding ◽  
Translocator Protein 18 Kda

scholarly journals In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence

2017 ◽  
Vol 22 (12) ◽  
pp. 1759-1766 ◽  
Author(s):  
A T Hillmer ◽  
C M Sandiego ◽  
J Hannestad ◽  
G A Angarita ◽  
A Kumar ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
In Vivo Imaging ◽  
Protein A ◽  
Translocator Protein ◽  
Activated Microglia

scholarly journals Identification of Koumine as a Translocator Protein 18 kDa Positive Allosteric Modulator for the Treatment of Inflammatory and Neuropathic Pain

2021 ◽  
Vol 12 ◽  
Author(s):  
Bojun Xiong ◽  
Guilin Jin ◽  
Ying Xu ◽  
Wenbing You ◽  
Yufei Luo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Therapeutic Target ◽  
Pain Treatment ◽  
Translocator Protein ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Pharmacological Characterization ◽  
Competitive Binding Assay ◽  
Translocator Protein 18 Kda

Koumine is an alkaloid that displays notable activity against inflammatory and neuropathic pain, but its therapeutic target and molecular mechanism still need further study. Translocator protein 18 kDa (TSPO) is a vital therapeutic target for pain treatment, and recent research implies that there may be allostery in TSPO. Our previous competitive binding assay hint that koumine may function as a TSPO positive allosteric modulator (PAM). Here, for the first time, we report the pharmacological characterization of koumine as a TSPO PAM. The results imply that koumine might be a high-affinity ligand of TSPO and that it likely acts as a PAM since it could delay the dissociation of 3H-PK11195 from TSPO. Importantly, the allostery was retained in vivo, as koumine augmented Ro5-4864-mediated analgesic and anti-inflammatory effects in several acute and chronic inflammatory and neuropathic pain models. Moreover, the positive allosteric modulatory effect of koumine on TSPO was further demonstrated in cell proliferation assays in T98G human glioblastoma cells. In summary, we have identified and characterized koumine as a TSPO PAM for the treatment of inflammatory and neuropathic pain. Our data lay a solid foundation for the use of the clinical candidate koumine to treat inflammatory and neuropathic pain, further demonstrate the allostery in TSPO, and provide the first proof of principle that TSPO PAM may be a novel avenue for the discovery of analgesics.

scholarly journals In Vivo Imaging of Translocator Protein in Long-term Cannabis Users

2019 ◽  
Vol 76 (12) ◽  
pp. 1305 ◽  
Author(s):  
Tania Da Silva ◽  
Sina Hafizi ◽  
Jeremy J. Watts ◽  
Cynthia Shannon Weickert ◽  
Jeffrey H. Meyer ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Translocator Protein
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