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Artykuły w czasopismach na temat „DPA-714”

Autor: Grafiati

Data publikacji: 2 czerwca 2025

Data aktualizacji: 31 lipca 2025

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1

Lin, Qianqian, Youliang Wang, Wenlong Zhao, and Shaobo Yao. "Visualization of Thromboinflammation by 18F-DPA-714 PET in a Stroke Patient." Clinical Nuclear Medicine 48, no. 10 (2023): e477-e479. http://dx.doi.org/10.1097/rlu.0000000000004803.

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Abstract A 44-year-old man who presented with progressive right limb weakness was diagnosed with ischemic stroke. He was referred for 18F-DPA-714 PET/CT for evaluation of the disease. 18F-DPA-714 PET/CT showed increased uptake of the intracranial thrombus. This DPA-714–avid thrombus highly suggested the involvement of immune cells in the extension of the clot resulting in neurological deterioration. This present case suggested that 18F-DPA-714 PET might be a promising tracer in visualizing thromboinflammation in vivo.

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Boutin, Hervé, Christian Prenant, Renaud Maroy, et al. "[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats." PLoS ONE 8, no. 2 (2013): e56441. https://doi.org/10.1371/journal.pone.0056441.

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<strong>Purpose: </strong>Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [18F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [18F]DPA-714, it was compared directly to [11C]PK11195 in experimental cerebral ischaemia in rats. <strong>Methods:</strong>

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3

Vicidomini, Caterina, Mariarosaria Panico, Adelaide Greco, et al. "In vivo imaging and characterization of [(18)F]DPA-714, a potential new TSPO ligand, in mouse brain and peripheral tissues using small-animal PET." Nucl Med Biol. 42, no. 3 (2014): 309–16. https://doi.org/10.1016/j.nucmedbio.2014.11.009.

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INTRODUCTION: The translocator protein 18kDa (TSPO), a biochemical marker of neuroinflammation, is highly expressed in the brain activated microglia and it is also expressed by peripheral inflammatory cells and normal peripheral tissues. Thus, development of radioligands for the TSPO may contribute to further understanding the in vivo TSPO function in central and peripheral inflammatory processes and other pathologies. Here, we report the biodistribution, the specific binding and the radiometabolites of [(18)F]DPA-714, a promising fluorinated PET radiotracer, in normal mice using a microP

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Zheng, Jinzi, Alexandra Winkeler, Marie-Anne Peyronneau, Frédéric Dollé, and Raphael Boisgard. "Evaluation of PET Imaging Performance of the TSPO Radioligand [18F]DPA-714 in Mouse and Rat Models of Cancer and Inflammation." Molecular Imaging and Biology 18, no. 1 (2015): 127–34. https://doi.org/10.1007/s11307-015-0877-x.

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PURPOSE: Many radioligands have been explored for imaging the 18-kDa translocator protein (TSPO), a diagnostic and therapeutic target for inflammation and cancer. Here, we investigated the TSPO radioligand [18F]DPA-714 for positron emission tomography (PET) imaging of cancer and inflammation. PROCEDURES: [18F]DPA-714 PET imaging was performed in 8 mouse and rat models of breast and brain cancer and 4 mouse and rat models of muscular and bowel inflammation. RESULTS: [18F]DPA-714 showed different uptake levels in healthy organs and malignant tissues of mice and rats. Although high and displaceab

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5

Zinnhardt, Bastian, Michael Müther, Wolfgang Roll, et al. "TSPO imaging-guided characterization of the immunosuppressive myeloid tumor microenvironment in patients with malignant glioma." Neuro-Oncology 22, no. 7 (2020): 1030–43. http://dx.doi.org/10.1093/neuonc/noaa023.

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Abstract Background Tumor-associated microglia and macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are potent immunosuppressors in the glioma tumor microenvironment (TME). Their infiltration is associated with tumor grade, progression, and therapy resistance. Specific tools for image-guided analysis of spatiotemporal changes in the immunosuppressive myeloid tumor compartments are missing. We aimed (i) to evaluate the role of fluorodeoxyglucose (18F)DPA-714* (translocator protein [TSPO]) PET-MRI in the assessment of the immunosuppressive TME in glioma patients, and (ii) to cross

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6

Golla, Sandeep SV, Ronald Boellaard, Vesa Oikonen, et al. "Quantification of [18F]DPA-714 Binding in the Human Brain: Initial Studies in Healthy Controls and Alzheimer'S Disease Patients." Journal of Cerebral Blood Flow & Metabolism 35, no. 5 (2015): 766–72. http://dx.doi.org/10.1038/jcbfm.2014.261.

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Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([18F] DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of [18F]DPA-714 binding in healthy subjects and Alzheimer's disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along with arte

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7

Ory, Dieter, Andrey Postnov, Michel Koole, et al. "Quantification of TSPO overexpression in a rat model of local neuroinflammation induced by intracerebral injection of LPS by the use of [(18)F]DPA-714 PET." Eur J Nucl Med Mol Imaging 43, no. 1 (2015): 163–72. https://doi.org/10.1007/s00259-015-3172-9.

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PURPOSE: [(18)F]DPA-714 is a radiotracer with high affinity for TSPO. We have characterized the kinetics of [(18)F]DPA-714 in rat brain and evaluated its ability to quantify TSPO expression with PET using a neuroinflammation model induced by unilateral intracerebral injection of lipopolysaccharide (LPS). METHODS: Dynamic small-animal PET scans with [(18)F]DPA-714 were performed in Wistar rats on a FOCUS-220 system for up to 3 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Full kinetic modelling of [(18)F]DPA-714 brain uptake was perfor

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8

Golla, Sandeep SV, Ronald Boellaard, Vesa Oikonen, et al. "Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients." Journal of Cerebral Blood Flow and Metabolism 35, no. 5 (2015): 766–72. https://doi.org/10.1038/jcbfm.2014.261.

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Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([18F]DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of [18F]DPA-714 binding in healthy subjects and Alzheimer's disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along

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9

Keller, Thomas, Anna Krzyczmonik, Sarita Forsback, et al. "Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats." Molecular Imaging & Biology 19, no. 5 (2017): 736–45. https://doi.org/10.1007/s11307-016-1040-z.

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PURPOSE: Many neurological conditions result in the overexpression of the translocator protein 18 kDa (TSPO), today recognized as a biomarker for microglial activation and neuroinflammation imaging. The pyrazolo[1,5-a]pyrimidine acetamides are a particularly attractive class of TSPO-specific ligands, prompting the development of several positron emission tomography (PET) radiotracers. This includes F-DPA, a recently reported fluorinated ligand (K <sub>i</sub> =&thinsp;1.7 nM), wherein the fluorine atom is directly linked to the phenyl moiety without the presence of an alky

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10

Werry, Eryn L., Victoria A. King, Melissa L. Barron, Samuel D. Banister, Renee Sokias, and Michael Kassiou. "Derivatives of the pyrazolo[1,5-a]pyrimidine acetamide DPA-713 as translocator protein (TSPO) ligands and pro-apoptotic agents in human glioblastoma." European Journal of Pharmaceutical Sciences 96 (September 19, 2016): 186–92. https://doi.org/10.1016/j.ejps.2016.09.026.

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The 18kDa translocator protein (TSPO) is a target for novel glioblastoma therapies due to its upregulation in this cancer and relatively low levels of expression in the healthy cortex. The pyrazolo[1,5-a]pyrimidine acetamides, exemplified by DPA-713 and DPA-714, are a class of high affinity TSPO ligands with selectivity over the central benzodiazepine receptor. In this study we have explored the potential anti-glioblastoma activity of a library of DPA-713 and DPA-714 analogues, and investigated the effect of amending the alkyl ether chain on TSPO affinity and functional potential. All ligands

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11

Awde, Ali R., Raphael Boisgard, Benoit Thézé, et al. "The Translocator Protein Radioligand 18F-DPA-714 Monitors Antitumor Effect of Erufosine in a Rat 9L Intracranial Glioma Model." Journal of Nuclear Medicine 54, no. 12 (2013): 2125–31. https://doi.org/10.2967/jnumed.112.118794.

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On the one hand, the translocator protein (TSPO) radioligand N,N-diethyl-2-(2-(4-(2-(18)F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ((18)F-DPA-714) has been suggested to serve as an alternative radiotracer to image human glioma, and on the other hand the alkylphosphocholine erufosine (ErPC3) has been reported to induce apoptosis in otherwise highly apoptosis-resistant glioma cell lines. The induction of apoptosis by ErPC3 requires TSPO, a mitochondrial membrane protein highly expressed in malignant gliomas. In this preclinical study, we monitored the effect of Er

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Bernards, Nicholas, Géraldine Pottier, Benoit Thézé, Frédéric Dollé та Raphael Boisgard. "In vivo Evaluation of Inflammatory Bowel Disease with the Aid of μPET and the Translocator Protein 18 kDa Radioligand [18F]DPA-714". Mol Imaging Biol 17 (2 липня 2014): 67–75. https://doi.org/10.1007/s11307-014-0765-9.

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Purpose: The purpose of the study was to validate [18F]DPA-714, a translocator protein (TSPO) 18 kDa radioligand, as a probe to non-invasively quantify the inflammatory state in inflammatory bowel disease (IBD) animal models. Procedures: Quantitative positron emission tomography (PET) imaging of intestinal inflammation was conducted with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) a glucose metabolism surrogate marker and [18F]DPA-714 a ligand of the 18 kDa TSPO, on two IBD models. The first model was induced using dextran sodium sulfate (DSS), creating global inflammat

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13

Martín, Abraham, Raphaël Boisgard, Benoit Thézé, et al. "Evaluation of the PBR/TSPO Radioligand [18F]DPA-714 in a Rat Model of Focal Cerebral Ischemia." Journal of Cerebral Blood Flow & Metabolism 30, no. 1 (2009): 230–41. http://dx.doi.org/10.1038/jcbfm.2009.205.

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Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [18F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. In vivo PET imaging showed signific

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Damont, Annelaure, Sébastien Garcia-Argote, David-Alexandre Buisson, Bernard Rousseau, and Frédéric Dollé. "Efficient tritiation of the translocator protein (18kDa) selective ligand DPA-714." J Labelled Comp Radiopharm. 58, no. 1 (2015): 1–6. https://doi.org/10.1002/jlcr.3252.

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DPA-714 (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) is a recently discovered fluorinated ligand of the translocator protein 18 kDa (TSPO). Labelled with the short-lived positron emitter fluorine-18, this structure is today the radioligand of reference for in vivo imaging of microglia activation and neuroinflammatory processes with positron emission tomography. In the present work, an isotopically tritium-labelled version was developed ([3H]DPA-714), in order to access high resolution in vitro and ex vivo microscopic auto

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Ricigliano, Vito A. G., Céline Louapre, Emilie Poirion, et al. "Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis." Neurology - Neuroimmunology Neuroinflammation 9, no. 6 (2022): e200026. http://dx.doi.org/10.1212/nxi.0000000000200026.

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Background and ObjectivesRecent imaging studies have suggested a possible involvement of the choroid plexus (CP) in multiple sclerosis (MS). Here, we investigated whether CP changes are already detectable at the earliest stage of MS, preceding symptom onset.MethodsThis study is a retrospective analysis of 27 patients with presymptomatic MS, 97 patients with clinically definite MS (CDMS), and 53 healthy controls (HCs) who underwent a cross-sectional 3T-MRI acquisition; of which, 22 MS, 19 HCs, and 1 presymptomatic MS (evaluated 8 months before conversion to CDMS) also underwent translocator pro

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Abourbeh, Galith, Benoit Thézé, Renaud Maroy, et al. "Imaging Microglial/Macrophage Activation in Spinal Cords of Experimental Autoimmune Encephalomyelitis Rats by Positron Emission Tomography Using the Mitochondrial 18kDa Translocator Protein Radioligand [18F]DPA-714." Journal of Neuroscience 32, no. 17 (2012): 5728–36. https://doi.org/10.1523/JNEUROSCI.2900-11.2012.

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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated microglia/macrophages play a key role in the immunopathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Microglia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of microglial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuroinflammatory processes. EAE was in

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Takkinen, Jatta S., Francisco R. López-Picón, Rana Al Majidi, et al. "Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging." Journal of Cerebral Blood Flow & Metabolism 37, no. 8 (2016): 2870–82. http://dx.doi.org/10.1177/0271678x16677990.

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Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer’s disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer’s disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer’s disease using longitudinal in vivo18F-FDG and 18F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n = 9) and wild type control mice (WT, n = 9) were st

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Médran-Navarrete, Vincent, Annelaure Damont, Marie-Anne Peyronneau, et al. "Preparation and evaluation of novel pyrazolo[1,5-a]pyrimidine acetamides, closely related to DPA-714, as potent ligands for imaging the TSPO 18 kDa with PET." Bioorg Med Chem Lett. 24, no. 6 (2014): 1550–6. https://doi.org/10.1016/j.bmcl.2014.01.080.

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A series of four novel analogues of DPA-714, bearing a fluoroalkynyl side chain (with a length ranging from three to six carbon atoms) in replacement of the fluoroethoxy motif, have been synthetized in six steps from commercially available methyl 4-iodobenzoate. The synthetic strategy for the preparation of these N,N-diethyl-2-(2-(4-(x-fluoroalk-1-ynyl)phenyl)-5,7 dimethylpyrazolo[1,5-a]pyrimidin-3- yl)acetamides (7a–d) consisted in derivatizing a key iodinated building block featuring the pyrazolopyrimidine acetamide backbone of DPA-714, by Sonogashira coup

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García-Lorenzo, Daniel, Sonia Lavisse, Claire Leroy, et al. "Validation of an automatic reference region extraction for the quantification of [18F]DPA-714 in dynamic brain PET studies." Journal of Cerebral Blood Flow & Metabolism 38, no. 2 (2017): 333–46. http://dx.doi.org/10.1177/0271678x17692599.

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There is a great need for a non-invasive methodology enabling the quantification of translocator protein overexpression in PET clinical imaging. [18F]DPA-714 has emerged as a promising translocator protein radiotracer as it is fluorinated, highly specific and returned reliable quantification using arterial input function. Cerebellum gray matter was proposed as reference region for simplified quantification; however, this method cannot be used when inflammation involves cerebellum. Here we adapted and validated a supervised clustering (supervised clustering algorithm (SCA)) for [18F]DPA-714 ana

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Golla, Sandeep SV, Ronald Boellaard, Vesa Oikonen, et al. "Parametric binding images of the TSPO ligand [18F]DPA-714." Journal of Nuclear Medecine 57, no. 10 (2016): 1543–47. https://doi.org/10.2967/jnumed.116.173013.

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Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide (<sup>18</sup>F-DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of <sup>18</sup>F-DPA-714 binding. METHODS: Ninety minutes dynamic <sup>18</sup>F-DPA-714 positron emission tomography scans with full arterial sampling from 6 healthy subjects and 9 Alzheimer's disease (AD) patients were used. Plasma input based Logan graphical and spectral (SA) a

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Cacheux, Fanny, Vincent Médran-Navarrete, Frédéric Dollé, Frank Marguet, Frédéric Puech, and Annelaure Damont. "Synthesis and in vitro characterization of novel fluorinated derivatives of the translocator protein 18 kDa ligand CfO-DPA-714." European Journal of Medicinal Chemistry 125 (September 9, 2016): 346–59. https://doi.org/10.1016/j.ejmech.2016.09.025.

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The translocator protein 18 kDa (TSPO) is today a validated target for a number of therapeutic applications, but also a well-recognized diagnostic/imaging biomarker for the evaluation of inflammatory related-disease state and progression, prompting the development of specific and dedicated TSPO ligands worldwide. For this purpose, pyrazolo[1,5-a]pyrimidine acetamides constitute a unique class of high affinity and selectivity TSPO ligands; it includes DPA-714, a fluorine-containing derivative that has also been labelled with the positron-emitter fluorine-18, and is nowadays widely used as

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Takkinen, Jatta S., Francisco R. López-Picón, Majidi Rana Al, et al. "Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging." Journal of Cerebral Blood Flow and Metabolism 37, no. 8 (2016): 2870–82. https://doi.org/10.1177/0271678X16677990.

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Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivo <sup>18</sup>F-FDG and <sup>18</sup>F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n =&am

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Sridharan, Sujata, Francois-Xavier Lepelletier, William Trigg, et al. "Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats." Molecular Imaging & Biology 19 (August 1, 2016): 77–89. https://doi.org/10.1007/s11307-016-0984-3.

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PURPOSE: Over the past 20 years, neuroinflammation (NI) has increasingly been recognised as having an important role in  many neurodegenerative diseases, including Alzheimer's disease. As such, being able to image NI non-invasively in patients is critical to monitor pathological processes and potential therapies targeting neuroinflammation. The translocator protein (TSPO) has proven a reliable NI biomarker for positron emission tomography (PET) imaging. However, if TSPO imaging in acute conditions such as stroke provides strong and reliable signals, TSPO imaging in neurodegenerat

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Gargiulo, S., S. Anzilotti, ARD Coda, et al. "Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with 18F-DPA-714 and micro-PET/CT." European Journal of Nuclear Medecine and Molecular Imaging 43, no. 7 (2016): 1348–59. https://doi.org/10.1007/s00259-016-3311-y.

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PURPOSE: To evaluate the feasibility and sensitivity of <sup>18</sup>F-DPA-714 for the study of microglial activation in the brain and spinal cord of transgenic SOD1<sup>G93A</sup> mice using high-resolution PET/CT and to evaluate the Iba1 and TSPO expression with immunohistochemistry. METHODS: Nine symptomatic SOD1<sup>G93A</sup> mice (aged 117 ± 12.7 days, clinical score range 1 - 4) and five WT SOD1 control mice (aged 108 ± 28.5 days) underwent <sup>18</sup>F-DPA-714 PET/CT. SUV ratios were calculated by normalizing the cerebella

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Gomes de Almeida Schirmer, Brígida, Juliana De Oliveira Silva, Douglas Boniek Silva Navarro, et al. "Assessment of basal TSPO expression and [18F]DPA-714 biodistribution in healthy mice and post-ischemic brain using PET imaging." Brazilian Journal of Radiation Sciences 12, no. 4A (Suppl.) (2025): e2812. https://doi.org/10.15392/2319-0612.2024.2812.

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Positron emission tomography (PET) is an important tool in preclinical studies in small animals, providing real-time insights into biochemical, metabolic, physiological, and functional processes. PET imaging also enables the assessment of biological responses and biodistribution of novel radiolabeled compounds within a single animal, minimizing the need for larger animal groups. In particular, PET imaging with [18F]DPA-714, a Translocator Protein (TSPO) ligand, has shown high predictive and prognostic value in diseases associated with neuroinflammation and correlates well with functional outco

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Fang, Yu-Hua Dean, Jonathan E. McConathy, Talene A. Yacoubian, Yue Zhang, Richard E. Kennedy, and David G. Standaert. "Image Quantification for TSPO PET with a Novel Image-Derived Input Function Method." Diagnostics 12, no. 5 (2022): 1161. http://dx.doi.org/10.3390/diagnostics12051161.

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There is a growing interest in using 18F-DPA-714 PET to study neuroinflammation and microglial activation through imaging the 18-kDa translocator protein (TSPO). Although quantification of 18F-DPA-714 binding can be achieved through kinetic modeling analysis with an arterial input function (AIF) measured with blood sampling procedures, the invasiveness of such procedures has been an obstacle for wide application. To address these challenges, we developed an image-derived input function (IDIF) that noninvasively estimates the arterial input function from the images acquired for 18F-DPA-714 quan

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Foucault-Fruchard, Laura, Aurélie Doméné, Guylene Page, et al. "Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model." Neuroscience 356 (May 18, 2017): 52–63. https://doi.org/10.1016/j.neuroscience.2017.05.019.

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Abstract Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. The link between nicotine intake and positive outcome has been established, suggesting a role played by nicotinic receptors (nAChRs), especially α7nAChRs. The objective of this study was to evaluate the potential dose effects of PHA 543613 on neuron survival and striatal microglial activation in a rat model of brain excitotoxicity. A preliminary study was performed in vitro to confirm PHA 543613 agonist properties on α7nAChRs. Rats were lesioned in the right striatum with quinolinic

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Banister, Samuel D., Corinne Beinat, Shane M. Wilkinson, et al. "Ether analogues of DPA-714 with subnanomolar affinity for the translocator protein (TSPO)." Eur J Med Chem. 93 (February 7, 2015): 392–400. https://doi.org/10.1016/j.ejmech.2015.02.004.

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Sixteen new phenyl alkyl ether derivatives (12, 14-28) of the 5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-ylacetamide (DPA) class were synthesized and evaluated in a competition binding assay against [3H]PK11195 using 18 kDa translocator protein (TSPO) derived from rat kidney mitochondrial fractions. All analogues showed superior binding affinities for TSPO compared to DPA-713 (5) and DPA-714 (6). Picomolar affinities were observed for this class of TSPO ligands in this assay for the first time, with phenethyl ether 28 showing the greatest affinity (Ki = 0.13 nM). Additiona

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Bocan, Thomas M., Robert G. Stafford, Jennifer L. Brown, et al. "Characterization of Brain Inflammation, Apoptosis, Hypoxia, Blood-Brain Barrier Integrity and Metabolism in Venezuelan Equine Encephalitis Virus (VEEV TC-83) Exposed Mice by In Vivo Positron Emission Tomography Imaging." Viruses 11, no. 11 (2019): 1052. http://dx.doi.org/10.3390/v11111052.

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Traditional pathogenesis studies of alphaviruses involves monitoring survival, viremia, and pathogen dissemination via serial necropsies; however, molecular imaging shifts this paradigm and provides a dynamic assessment of pathogen infection. Positron emission tomography (PET) with PET tracers targeted to study neuroinflammation (N,N-diethyl-2-[4-phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide, [18F]DPA-714), apoptosis (caspase-3 substrate, [18F]CP-18), hypoxia (fluormisonidazole, [18F]FMISO), blood–brain barrier (BBB) integrity ([18F]albumin), and metabolism (fluorodeoxyglucose, [18

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Ory, Dieter, Anna Planas, Tom Dresselaers, et al. "PET imaging of TSPO in a rat model of local neuroinflammation induced by intracerebral injection of lipopolysaccharide." Nucl Med Biol. 42, no. 10 (2015): 753–61. https://doi.org/10.1016/j.nucmedbio.2015.06.010.

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OBJECTIVE: The goal of this study was to measure functional and structural aspects of local neuroinflammation induced by intracerebral injection of lipopolysaccharide (LPS) in rats using TSPO microPET imaging with [(18)F]DPA-714, magnetic resonance imaging (MRI), in vitro autoradiography and immunohistochemistry (IHC) in order to characterize a small animal model for screening of new PET tracers targeting neuroinflammation. METHODS: Rats were injected stereotactically with LPS (50 μg) in the right striatum and with saline in the left striatum. [(18)F]DPA-714 microPET, MRI, in vitro autoradi

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Golla, S. S. V., R. Boellaard, V. Oikonen, et al. "Parametric Binding Images of the TSPO Ligand 18F-DPA-714." Journal of Nuclear Medicine 57, no. 10 (2016): 1543–47. http://dx.doi.org/10.2967/jnumed.116.173013.

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Park, Jaekyung, Sobia Wasim, Jae Ho Jung, et al. "Synthesis, In Silico and In Vitro Characterization of Novel N,N-Substituted Pyrazolopyrimidine Acetamide Derivatives for the 18KDa Translocator Protein (TSPO)." Pharmaceuticals 16, no. 4 (2023): 576. http://dx.doi.org/10.3390/ph16040576.

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The translocator protein (TSPO) is an interesting biological target for molecular imaging and therapy because the overexpression of TSPO is associated with microglial activation caused by neuronal damage or neuroinflammation, and these activated microglia are involved in various central nervous system (CNS) diseases. The TSPO is a target for neuroprotective treatment, which is used with the aim of reducing microglial cell activation. The novel N,N-disubstituted pyrazolopyrimidine acetamides scaffold (GMA 7–17), which bears a fluorine atom and is directly linked to the phenyl moiety, was synthe

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Cheval, Margaux, Sebastian Rodrigo, Claire Leroy, et al. "[18F]DPA-714 PET Imaging in the Presurgical Evaluation of Patients With Drug-Resistant Focal Epilepsy." Neurology, September 25, 2023. http://dx.doi.org/10.1212/wnl.0000000000207811.

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Background and Objective: Translocator protein 18 kDa (TSPO) positron emission tomography (PET) imaging is used to monitor glial activation. Recent studies have proposed TSPO PET as a marker of the epileptogenic zone (EZ) in drug-resistant focal epilepsy (DRFE). This study aims to assess the contributions of TSPO imaging using [18F]DPA-714 PET and [18F]FDG PET for localizing the EZ during pre-surgical assessment of DRFE, when phase 1 pre-surgical assessment does not provide enough information. Methods: We compared [18F]FDG and [18F]DPA-714 PET images of 23 patients who had undergone a phase 1

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"Synthesis of DPA-714." Synfacts 8, no. 10 (2012): 1050. http://dx.doi.org/10.1055/s-0032-1316982.

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López-Picón, Francisco R., Thomas Keller, Diana Bocancea, et al. "Direct Comparison of [18F]F-DPA with [18F]DPA-714 and [11C]PBR28 for Neuroinflammation Imaging in the same Alzheimer’s Disease Model Mice and Healthy Controls." Molecular Imaging and Biology, September 20, 2021. http://dx.doi.org/10.1007/s11307-021-01646-5.

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Abstract Purpose In this study we compared the recently developed TSPO tracer [18F]F-DPA, with [18F]DPA-714 and [11C]PBR28 by performing in vivo PET imaging on the same Alzheimer’s disease mouse model APP/PS1-21 (TG) and wild-type (WT) mice with all three radiotracers. Procedures To compare the radiotracer uptake, percentage of injected dose/mL (%ID/mL), standardized uptake value ratios to cerebellum (SUVRCB), and voxel-wise analyses were performed. Results The peak uptake of [18F]F-DPA was higher than 4.3% ID/mL, while [18F]DPA-714 reached just over 3% ID/mL, and [11C]PBR28 was over 4% ID/mL

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Ribeiro, Maria-Joao, Johnny Vercouillie, Severine Debiais, et al. "Could (18) F-DPA-714 PET imaging be interesting to use in the early post-stroke period?" EJNMMI Research 4 (June 6, 2014). https://doi.org/10.1186/s13550-014-0028-4.

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BACKGROUND: Cerebral stroke is a severe and frequent condition that requires rapid and reliable diagnosis. If administered shortly after the first symptoms manifest themselves, IV thrombolysis has been shown to increase the functional prognosis by restoring brain reperfusion. However, a better understanding of the pathophysiology of stroke should help to identify potential new therapeutic targets. Stroke is known to induce an inflammatory brain reaction that involves overexpression of the 18-kDa translocator protein (TSPO) in glial cells and infiltrated leukocytes, which can be visualised by p

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Cybulska, Klaudia A., Vera Bloemers, Lars R. Perk, and Peter Laverman. "Optimised GMP-compliant production of [18F]DPA-714 on the Trasis AllinOne module." EJNMMI Radiopharmacy and Chemistry 6, no. 1 (2021). http://dx.doi.org/10.1186/s41181-021-00133-0.

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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 repo

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Zhang, Siqi, Jie Hu, Zhigang Qi, et al. "Hybrid PET/MRI Imaging of 18F‐Fluorodeoxyglucose and 18‐kDa Translocator Protein for Presurgical Localization in Refractory Epilepsy." CNS Neuroscience & Therapeutics 31, no. 2 (2025). https://doi.org/10.1111/cns.70251.

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ABSTRACTPurposeSurgery remains the only curative option for a third of refractory epilepsy patients, though success depends on precise localization of the epileptogenic zone (EZ). This study aims to assess the clinical value of hybrid 18F‐FDG and 18F‐DPA‐714 PET/MRI for accurate localization and precise boundary delineation.MethodsThe refractory epilepsy patients who underwent surgery at Xuanwu Hospital from November 2022 to November 2023 were retrospectively recruited. Preoperative simultaneous 18F‐FDG and 18F‐DPA‐714 PET/MRI imaging were analyzed using the asymmetry index (AI) and a 4‐point

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Clément, Alexandra, Timothee Zaragori, Romain Filosa, et al. "Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study." Cancer Imaging 22, no. 1 (2022). http://dx.doi.org/10.1186/s40644-022-00454-6.

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Abstract Background This translational study explores multi-tracer PET imaging for the non-invasive detection of the IDH1 mutation which is a positive prognostic factor in glioma. Methods U87 human high-grade glioma (HGG) isogenic cell lines with or without the IDH1 mutation (CRISP/Cas9 method) were stereotactically grafted into rat brains, and examined, in vitro, in vivo and ex vivo. PET imaging sessions, with radiotracers specific for glycolytic metabolism ([18F]FDG), amino acid metabolism ([18F]FDopa), and inflammation ([18F]DPA-714), were performed sequentially during 3–4 days. The in vitr

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Pottier, Géraldine, Nicholas Bernards, Frédéric Dollé, and Raphael Boisgard. "[18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model." Arthritis Research & Therapy 16, R69 (2014). https://doi.org/10.1186/ar4508.

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Abstract Introduction: Rheumatoid arthritis (RA) is a chronic disease, affecting 0.5 to 1% of adults in industrialized countries, in which systemic inflammation and synovitis drive joint destruction. [18F]DPA-714 is a specific tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of neuroinflammation. Today, diagnosis of patients with early inflammatory arthritis is limited by poor sensitivity and specificity. The present study aims to investigate the potential of [18F]DPA-714 to monitor in vivo inflam

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Zinnhardt, Bastian, Michael Müther, Wolfgang Roll, et al. "TSPO imaging-guided characterization of the immunosuppressive myeloid tumor microenvironment in patients with malignant glioma." February 12, 2020. https://doi.org/10.1093/neuonc/noaa023.

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<strong>Abstract</strong> <strong>Background</strong>: Tumor-associated microglia and macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are potent immunosuppressors in the glioma tumor microenvironment (TME). Their infiltration is associated with tumor grade, progression and therapy resistance. Specific tools for image-guided analysis of spatio-temporal changes in the immunosuppressive myeloid tumor compartments are missing. We aimed (i) to evaluate the role of [<sup>18</sup>F]DPA-714 (TSPO) PET-MRI in the assessment of the immunosuppressive TME in glioma patients and (ii) to cro

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Martinez-Orengo, Neysha, Sarine Tahmazian, Jianhao Lai, et al. "Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging." Frontiers in Immunology 13 (November 10, 2022). http://dx.doi.org/10.3389/fimmu.2022.1010263.

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There is current need for new approaches to assess/measure organ-level immunoreactivity and ensuing dysfunction in systemic inflammatory response syndrome (SIRS) and sepsis, in order to protect or recover organ function. Using a rat model of systemic sterile inflammatory shock (intravenous LPS administration), we performed PET imaging with a translocator protein (TSPO) tracer, [18F]DPA-714, as a biomarker for reactive immunoreactive changes in the brain and peripheral organs. In vivo dynamic PET/CT scans showed increased [18F]DPA-714 binding in the brain, lungs, liver and bone marrow, 4 hours

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Kong, Xiang, Song Luo, Yun Fei Wang, Gui Fen Yang, Guang Ming Lu, and Long Jiang Zhang. "[18F]PBR146 and [18F]DPA-714 in vivo Imaging of Neuroinflammation in Chronic Hepatic Encephalopathy Rats." Frontiers in Neuroscience 15 (August 16, 2021). http://dx.doi.org/10.3389/fnins.2021.678144.

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Neuroinflammation is an important pathogenesis of hepatic encephalopathy (HE). The upregulation of translocator protein (TSPO) during neuroinflammation provides an imaging molecular target to evaluate the severity of neuroinflammation in chronic HE rats. [18F]DPA-714 and [18F]PBR146 targeting TSPO are often used for neuroinflammation imaging. This study performed bile duct ligation (BDL) in rats to simulate chronic HE model, tested the behavioral experiments, and conducted [18F]PBR146 and [18F]DPA-714 micro-PET/CT scans followed analyzing the average %ID/g values of the whole brain, brain regi

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Godefroy, Thomas, Nicolas Arlicot, Olivier Kerdraon, et al. "Faisability pilot study to explore inflammation with 18F-DPA-714 PET CT versus immunochemistry in triple negative breast cancer: Design protocol." Archives of Clinical Trials, December 30, 2021. http://dx.doi.org/10.33425/2768-4598.1009.

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The Triple Negative Breast Cancer (TNBC), despite a good initial response to conventional chemotherapy, relapses frequently and has a poor prognosis after the onset of metastases. It is therefore interesting to develop new relevant targets to establish a prognosis but also potentially to propose a targeted therapy for a theranostic approach. A high density of M2-type macrophages presence in the primary TNBC tumor predicted an unfavorable prognosis. The presence of activated M2-type macrophages can be evaluated by measuring the expression of a translocating protein (TSPO) with [18F]-DPA-714 PET

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Liu, Yu, Lizhen Wang, Donghui Pan, et al. "PET evaluation of light-induced modulation of microglial activation and GLP-1R expression in depressive rats." Translational Psychiatry 11, no. 1 (2021). http://dx.doi.org/10.1038/s41398-020-01155-z.

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AbstractLight therapy has been accepted as a promising therapeutic choice for depression. Positron emission tomography (PET) combined with specific radiotracers has great benefits for revealing pathogenesis and developing therapeutics. This study aimed to investigate the influences of light therapy on microglial activation and glucagon-like peptide-1 receptor (GLP-1R) expression in the brain of depressive rats using [18F]DPA-714 and [18F]exendin-4 PET. The results showed that chronic unpredictable mild stress (CUMS)-induced depressive rats had poorer performance in behavioral tests compared to

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Rejc, Luka, Vanessa Gómez-Vallejo, Ana Joya, et al. "Longitudinal evaluation of neuroinflammation and oxidative stress in a mouse model of Alzheimer disease using positron emission tomography." Alzheimer's Research & Therapy 14, no. 1 (2022). http://dx.doi.org/10.1186/s13195-022-01016-5.

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Abstract Background Validation of new biomarkers of Alzheimer disease (AD) is crucial for the successful development and implementation of treatment strategies. Additional to traditional AT(N) biomarkers, neuroinflammation biomarkers, such as translocator protein (TSPO) and cystine/glutamine antiporter system (xc-), could be considered when assessing AD progression. Herein, we report the longitudinal investigation of [18F]DPA-714 and [18F]FSPG for their ability to detect TSPO and xc- biomarkers, respectively, in the 5xFAD mouse model for AD. Methods Expression of TSPO and xc- system was assess

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Barca, Cristina, Claudia Foray, Sven Hermann, et al. "Characterization of the inflammatory post-ischemic tissue by full volumetric analysis of a multimodal imaging dataset." November 1, 2020. https://doi.org/10.1016/j.neuroimage.2020.117217.

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ABSTRACT Introduction: In vivo positron emission tomography (PET) and magnetic resonance imaging (MRI) support non-invasive assessment of the spatiotemporal expression of proteins of interest and functional/structural changes. Our work promotes the use of a volumetric analysis on multimodal imaging datasets to assess the spatio-temporal dynamics and interaction of two imaging biomarkers, with a special focus on two neuroinflammation-related biomarkers, the translocator protein (TSPO) and matrix metalloproteinases (MMPs), in the acute and chronic post-ischemic phase. Aim: To improve our underst

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Foray, Claudia, Cristina Barca, Alexandra Winkeler, et al. "Interrogating Glioma-Associated Microglia and Macrophage Dynamics Under CSF-1R Therapy with Multitracer In Vivo PET/MRI." January 1, 2021. https://doi.org/10.2967/jnumed.121.263318.

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<strong>Abstract</strong> Glioma-associated microglia and macrophages (GAMMs) are key players in creating an immunosuppressive microenvironment. They can be efficiently targeted by inhibiting the colony-stimulating factor 1 receptor (CSF-1R). We applied noninvasive PET/CT and PET/MRI using 18F-fluoroethyltyrosine (18F-FET) (amino acid metabolism) and N,N-diethyl-2-[4-(2-18F-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo [1,5-a]pyrimidine-3-acetamide (18F-DPA-714) (translocator protein) to understand the role of GAMMs in glioma initiation, monitor in vivo therapy-induced GAMM depletion, and observe

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Li, Danxi, Di Hu, Yuta Ochi, et al. "Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats." Frontiers in Immunology 14 (November 9, 2023). http://dx.doi.org/10.3389/fimmu.2023.1261256.

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IntroductionA series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context of various infections, such as COVID-19. Although the pathogenic mechanisms underlying an infection causing fever and pain have been well established, the mechanisms of fatigue induced by infection in specific brain regions remain unclear.MethodsTo elucidate whether and how the peripheral infection cause fatigue via regional neuroinflammation, we performed a brain-wide investigation of neuroinflammation in a peripheral pseudoinfection rat model using [18F]

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Gallus, Marco, Wolfgang Roll, Andre Dik, et al. "Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell–mediated limbic encephalitis." Science Advances 9, no. 23 (2023). http://dx.doi.org/10.1126/sciadv.abq7595.

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Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral and cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were found. Assessment of such patients presents a clinical challenge, and novel noninvasive imaging biomarkers are urgently needed. Here, we demonstrate that visualization of the translocator protein (TSPO) with [ 18 F]DPA-714-PET-MRI reveals pronounced microglia activation and reactive gliosis in the

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