WORK PACKAGE 5

Validation of new probes for NIND in animal models

Sixteen INMiND partner institutions from ten countries (Austria, Belgium, Denmark, France, Germany, Hungary, Italy, Spain, Sweden, United Kingdom) are involved in the research activities of this work package. Leader of this work package is Anna PLANAS, head of the Experimental MRI Unit and leader of the Cerebrovascular Research team at IDIBAPS (Spain).

The main objectives of this work package are:

  • non-invasively assess NI in various animal models using existing PET probes to conclude on the best tracers to image NI providing data for quantification (WP7) and linking with studies in WP8
  • to validate NI findings against ex vivo and in vitro signs of microglial activation
  • to image NI with newly developed probes generated in WP3/4
  • to validate imaging findings of NI against markers of signs of ND and effects of treatments
  • to test and validate new reporter mice generated in WP1/2

WP5 Related papers


Epub ahead of print

Szőllősi D, Hegedűs N, Veres SD, Futó I, Horvath I, Kovacs N, Martinecz B, Dénes Á, Seifert D, Bergmann R, Lebeda O, Varga Z, Kaleta Z, Szigeti K, Máthé D. Evaluation of Brain Nuclear Medicine Imaging Tracers in a Murine Model of Sepsis Associated Encephalopathy. Mol Imaging Biol. 2018 May 7; epub ahead of print.
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2018

Beckers L, Ory D, Geric I, Declercq L, Koole M, Kassiou M, Bormans G, Baes M. Increased expression of translocator protein (TSPO) marks pro-inflammatory microglia but does not predict neurodegeneration. Mol Imaging Biol. 2018;20(1):94-102.
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Foucault-Fruchard L, Tronel C, Bodard S, Gulhan Z, Busson J, Chalon S, Antier D. Involvement of heme oxygenase-1 in neuroprotective effects induced by an alpha 7 nicotinic receptor agonist in a rat model of brain excitotoxicity. Neural Regen Res. 2018;13(4):737-741.
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Greco A, Zannetti A, Pappatà S, Albanese A, Coda AR, Ragucci M, Nardelli A, Brunetti A, Cuocolo A, Salvatore M. Measurement of [123I]FP-CIT binding to the dopamine transporter (DAT) in healthy mouse striatum using dedicated small animal SPECT imaging: feasibility, optimization and validation. Q J Nucl Med Mol Imaging. 2018;62(1):112-117.
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Muñoz-Moreno E, Tudela R, López-Gil X, Soria G. Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease. Alzheimers Res Ther;10(1):16.
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Wiesmann M, Zinnhardt B, Reinhardt D, Eligehausen S, Wachsmuth L, Hermann S, Dederen PJ, Hellwich M, Kuhlmann MT, Broersen LM, Heerschap A, Jacobs AH, Kiliaan AJ. A specific dietary intervention to restore brain structure and function after ischemic stroke. Theranostics 2017;7(2): 493-512.
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Zinnhardt B, Wiesmann M, Honold L, Barca C, Schäfers M, Kiliaan AJ, Jacobs AH. In vivo imaging biomarkers of neuroinflammation in the development and assessment of stroke therapies – towards clinical translation. Theranostics 2018;8(10):2603-2620.
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2017

Belloli S, Pannese M, Buonsanti C, Maiorino C, Di Grigoli G, Carpinelli A, Monterisi C, Moresco RM, Panina-Bordignon P. Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice. Neurobiol Aging. 2017;53:159-168.
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Cerami C, Iaccarino L, Perani D. Molecular imaging of neuroinflammation in neurodegenerative dementias: The role of in vivo PET imaging. Int J Mol Sci. 2017;18(5).
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Foucault-Fruchard L, Doméné A, Page G, Windsor M, Emond P, Rodrigues N, Dollé F, Damont A, Buron F, Routier S, Chalon S, Antier D. Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model. Neuroscience. 2017;356:52-63.
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Gargiulo S, Coda AR, Panico M, Gramanzini M, Moresco RM, Chalon S, Pappatà S. Molecular imaging of neuroinflammation in preclinical rodent models using positron emission tomography. Q J Nucl Med Mol Imaging 2017;61:60-75.
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Pongor CI, Bianco P, Ferenczy G, Kellermayer R, Kellermayer M. Optical trapping nanometry of hypermethylated CPG-Island DNA. Biophys J. 2017;112(3):512-522.
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Pottier G, Gómez-Vallejo V, Padro D, Boisgard R, Dollé F, Llop J, Winkeler A, Martin A. PET imaging of cannabinoid type 2 receptors with [11C]A-836339 did not evidence changes following. J Cereb Blood Flow Metab. 2017;37(3):1163-1178.
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Sridharan S, Lepelletier FX, Trigg W, Banister S, Reekie T, Kassiou M, Gerhard A, Hinz R, Boutin H. Comparative evaluation of three TSPO PET radiotracers in a LPS-induced model of mild neuroinflammation in rats. Mol Imaging Biol. 2017;19(1):77-89.
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Wiesmann M, Zinnhardt B, Reinhardt D, Eligehausen S, Wachsmuth L, Hermann S, Dederen PJ, Hellwich M, Kuhlmann MT, Broersen LM, Heerschap A, Jacobs AH, Kiliaan AJ. A specific dietary intervention to restore brain structure and function after ischemic stroke. Theranostics 2017;7(2): 493-512.
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Willekens SM, Van Weehaeghe D, Van Damme P, Van Laere K. Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks. Eur J Nucl Med Mol Imaging. 2017;44(3):533-547.
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Zinnhardt B, Pigeon H, Thézé B, Viel T, Wachsmuth L, Fricke IB, Schelhaas S, Honold L, Schwegmann K, Wagner S, Faust A, Faber C, Kuhlmann MT, Hermann S, Schäfers M, Winkeler A, Jacobs AH. Combined PET imaging of the inflammatory tumor microenvironment identifies margins of unique radiotracer uptake. Cancer Res. 2017;77(8):1831-1841.
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2016

Doméné A, Cavanagh C, Page G, Bodard S, Klein C, Delarasse C, Chalon S, Krantic S. Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer's Disease versus Age-Matched Controls: A Presymptomatic Stage Study. Int J Alzheimers Dis. 2016;2016:5696241.
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Donat CK, Gaber K, Meixensberger J, Brust P, Pinborg  LH, Hansen HH, Mikkelsen JD. Changes in binding of [123I]Clinde, a high-affinity translocator protein 18 kDa (TSPO) selective radioligand in a rat model of traumatic brain injury. Neuromolecular Med. 2016;18(2):158-69.
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Dupont AC, Guilloteau D, Kassiou M, Ribeiro MJ, Vercouillie J, Katsifis A, Arlicot N. Radiopharmaceuticals for PET imaging of neuroinflammation - Les radiopharmaceutiques pour l’imagerie TEP de la neuroinflammation. Médecine Nucléaire. 2016;40(1):72-81.
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Fricke IB, Viel T, Worlitzer MM, Collmann FM, Vrachimis A, Faust A, Wachsmuth L, Faber C, Dollé F, Kuhlmann MT, Schäfers K, Hermann S, Schwamborn JC, Jacobs AH. 6-hydroxydopamine-induced Parkinson’s disease-like degeneration generates acute micro- and astrogliosis in the nigrostriatal system but no Bioluminescence Imaging detectable alteration in adult neurogenesis. Eur J Neurosci. 2016;43(10):1352-65.
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Guglielmetti C, Le Blon D, Santermans E, Salas-Perdomo A, Daans J, De Vocht N, Shah D, Hoornaert C, Praet J, Peerlings J, Kara F, Bigot C, Mai Z, Goossens H, Hens N, Hendrix S, Verhoye M, Planas AM, Berneman Z, van der Linden A, Ponsaerts P. Interleukin-13 immune gene therapy prevents CNS inflammation and demyelination via alternative activation of microglia and macrophages. Glia. 2016;64(12):2181-2200.
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Kumar R, Nordberg A, Darreh-Shori T. Amyloid-β peptides act as allosteric modulators of cholinergic signalling through formation of soluble BAβACs. Brain. 2016;139(Pt 1):174-92.
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Ludewig P, Gallizioli M, Urra X, Behr S, Brait VH, Gelderblom M, Magnus T, Planas AM. Dendritic cells in brain diseases. Biochim Biophys Acta. 2016;1862(3):352-67.
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Miro-Mur F, Perez-de-Puig I, Ferrer-Ferrer M, Urra X, Justicia C, Chamorro A, Planas AM. Immature monocytes recruited to the ischemic mouse brain differentiate into macrophages with features of alternative activation.  Brain Behav Immun. 2016;53:18-33.
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Ory D, Postnov A, Koole M, Celen S, de Laat B, Verbruggen A, Van Laere K, Bormans G, Casteels C. Quantification of TSPO overexpression in a rat model of local neuroinflammation induced by intracerebral injection of LPS by the use of [18F]DPA-714 PET. Eur J Nucl Med Mol Imaging. 2016;43(1):163-72.
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Thomas C, Vercouillie J, Doméné A , Tauber C, Kassiou M, Guilloteau D, Destrieux C, Sérrière S,  Chalon S. Detection of neuroinflammation in a rat model of subarachnoid hemorrhage  using [18F]DPA-714 PET imaging. Mol Imaging. 2016 26;15. pii: 1536012116639189.
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Tóth M, Little P, Arnberg F, Häggkvist J, Mulder J, Halldin C, Gulyás B, Holmin S. Acute neuroinflammation in a clinically relevant focal cortical ischemic stroke model in rat: Longitudinal imaging of a focal cortical stroke model with [11C]PBR28 in rat. Brain Struct Funct. 2016;221(3):1279-90.
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Zheng J, Winkeler A, Peyronneau MA, Dollé F, Boisgard R. Evaluation of PET imaging performance of the TSPO radioligand [18F]DPA-714 in mouse and rat models of cancer and inflammation. Mol Imaging Biol. 2016;18(1):127-34.
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2015

Bernards N, Pottier G, Thézé B, Dollé F, Boisgard R. 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. 2015;17:67-75.
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Boutin H, Murray K, Pradillo J, Maroy R, Smigova A, Gerhard A, Jones PA, Trigg W. [18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke. Eur J Nucl Med Mol Imaging. 2015;42(3):503-11.
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Di Grigoli G, Monterisi C, Belloli S, Masiello V, Politi LS, Valenti S, Paolino M, Anzini M, Matarrese M, Cappelli A, Moresco RM. Radiosynthesis and preliminary biological evaluation of [18F]VC701, a radioligand for translocator protein. Mol Imaging. 2015;14:1535-3508.
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Farde L. Spotlight: TSPO binding may also represent ‘resting’ microglia. Clin Transl Imaging. 2015;3(6):491-492.
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Peelaerts W, Bousset L, Van der Perren A, Moskalyuk A, Pulizzi R, Giugliano M, Van den Haute C, Melki R, Baekelandt V. α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature. 2015;522(7556):340-4.
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Perez-de-Puig I, Miró-Mur F, Ferrer-Ferrer M, Gelpi E, Pedragosa J, Justicia C, Urra X, Chamorro A, Planas AM. Neutrophil recruitment to the brain in mouse and human ischemic stroke. Acta Neuropathol. 2015;129(2):239-57.
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Planas AM. Immunomodulatory role of IL-33 counteracts brain inflammation in stroke. Brain Behav Immun. 2015;50:39-40.
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Sérrière S, Doméné A , Vercouillie J, Mothès C, Bodard S, Rodrigues N, Guilloteau D, Routier S, Page G, Chalon S. Assessment of the protection of dopaminergic neurons by an α7 nicotinic receptor agonist, PHA 543613 using [18F]LBT-999 in a Parkinson's disease rat model. Front Med. 2015;2:61.
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Sérrière S, Tauber C , Vercouillie J, Mothès C, Pruckner C, Guilloteau D, Kassiou M, Doméné A, Garreau L, Page G, Chalon S. Amyloid load and translocator protein 18 kDa in APPswePS1-dE9 mice: a longitudinal study. Neurobiol Aging. 2015;36(4):1639-52.
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Szigeti K, Horváth I, Veres DS, Martinecz B, Lénárt N, Kovács N, Bakcsa E, Márta A, Semjéni M, Máthé D, Dénes Á. A novel SPECT-based approach reveals early mechanisms of central and peripheral inflammation after cerebral ischemia. J Cereb Blood Flow Metab. 2015;35(12):1921-9.
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Tóth M, Doorduin J, Häggkvist J, Varrone A, Amini N, Halldin C, Gulyás B. Positron Emission Tomography studies with [11C]PBR28 in the healthy rodent brain: Validating SUV as an outcome measure of neuroinflammation. PLoS One. 2015;10(5):e0125917.
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Verkhratsky A, Marutle A, Rodriguez-Arellano JJ, Nordberg A. Glial asthenia and functional paralysis: a new perspective on neurodegeneration and Alzheimer´s disease. Neuroscientist. 2015;21(5):552-568.
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Pottier G, Bernards N, Dollé F, Boisgard R. [18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model. Arthritis Res Ther. 2014;16(2):R69.
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Casteels C, Vunckx K, Aelvoet SA, Baekelandt V, Bormans G, Van Laere K, Koole M. Construction and evaluation of quantitative small-animal PET probabilistic atlases for [¹⁸F]FDG and [¹⁸F]FECT functional mapping of the mouse brain. PLoS One. 2013;8(6):e65286.
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