title: Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with (18)F-DPA-714 and micro-PET/CT.
abstract: OBJECTIVE
  To evaluate the feasibility and sensitivity of (18)F-DPA-714 for the study of microglial activation in the brain and spinal cord of transgenic SOD1(G93A) mice using high-resolution PET/CT and to evaluate the Iba1 and TSPO expression with immunohistochemistry.
  
  
  METHODS
  Nine symptomatic SOD1(G93A) mice (aged 117 ± 12.7 days, clinical score range 1 - 4) and five WT SOD1 control mice (aged 108 ± 28.5 days) underwent (18)F-DPA-714 PET/CT. SUV ratios were calculated by normalizing the cerebellar (rCRB), brainstem (rBS), motor cortex (rMCX) and cervical spinal cord (rCSC) activities to that of the frontal association cortex. Two WT SOD1 and six symptomatic SOD1(G93A) mice were studied by immunohistochemistry.
  
  
  RESULTS
  In the symptomatic SOD1(G93A) mice, rCRB, rBS and rCSC were increased as compared to the values in WT SOD1 mice, with a statistically significantly difference in rBS (2.340 ± 0.784 vs 1.576 ± 0.287, p = 0.014). Immunofluorescence studies showed that TSPO expression was increased in the trigeminal, facial, ambiguus and hypoglossal nuclei, as well as in the spinal cord, of symptomatic SOD1(G93A) mice and was colocalized with increased Iba1 staining.
  
  
  CONCLUSIONS
  Increased (18)F-DPA-714 uptake can be detected with high-resolution PET/CT in the brainstem of transgenic SOD1(G93A) mice, a region known to be a site of degeneration and increased microglial activation in amyotrophic lateral sclerosis, in agreement with increased TSPO expression in the brainstem nuclei shown by immunostaining. Therefore, (18)F-DPA-714 PET/CT might be a suitable tool to evaluate microglial activation in the SOD1(G93A) mouse model.
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.|Ceinge Biotecnologie Avanzate s. c. a r. l., Via G. Salvatore 486, 80145, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gargiulo
authors.affiliation: IRCCS SDN, Via E. Gianturco 113, 80143, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Anzilotti
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.
authors.forename: A R D
authors.initials: AR
authors.lastname: Coda
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.|Ceinge Biotecnologie Avanzate s. c. a r. l., Via G. Salvatore 486, 80145, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gramanzini
authors.affiliation: Ceinge Biotecnologie Avanzate s. c. a r. l., Via G. Salvatore 486, 80145, Naples, Italy.|Department of Advanced Biomedical Sciences, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Greco
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Panico
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Vinciguerra
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zannetti
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Vicidomini
authors.affiliation: CEA, Institute for Biomedical Imaging, 4 Place du Général Leclerc, 91401, Orsay, France.
authors.forename: F
authors.initials: F
authors.lastname: Dollé
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pignataro
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Quarantelli
authors.affiliation: IRCCS SDN, Via E. Gianturco 113, 80143, Naples, Italy.|Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Annunziato
authors.affiliation: Ceinge Biotecnologie Avanzate s. c. a r. l., Via G. Salvatore 486, 80145, Naples, Italy.|Department of Advanced Biomedical Sciences, University "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Brunetti
authors.affiliation: IRCCS SDN, Via E. Gianturco 113, 80143, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Salvatore
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy. sabina.pappata@ibb.cnr.it.
authors.forename: S
authors.initials: S
authors.lastname: Pappatà
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001835:Body Weight; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D000072078:Positron Emission Tomography Computed Tomography; D011720:Pyrazoles / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*
chemical_list: C463819:Bzrp protein, mouse; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA
keywords: 18F-DPA-714; PET/CT; SOD1G93A; TSPO; mice
references.citation: J Proteome Res. 2014 Apr 4;13(4):1800-9
references.pmid: 24579824
references.citation: J Neurosci. 2012 Apr 25;32(17 ):5728-36
references.pmid: 22539835
references.citation: Glia. 2002 Nov;40(2):206-17
references.pmid: 12379908
references.citation: Neurobiol Dis. 2010 Feb;37(2):370-83
references.pmid: 19874893
references.citation: J Cereb Blood Flow Metab. 2012 Jul;32(7):1393-415
references.pmid: 22549622
references.citation: Eur J Neurosci. 2004 Oct;20(7):1745-51
references.pmid: 15379995
references.citation: Neuroimage. 2012 May 1;60(4):2144-57
references.pmid: 22387126
references.citation: J Neuropathol Exp Neurol. 2008 Oct;67(10 ):1001-10
references.pmid: 18800007
references.citation: Brain Res Mol Brain Res. 1998 Jun 1;57(1):1-9
references.pmid: 9630473
references.citation: Biochem Biophys Res Commun. 2001 Aug 17;286(2):292-7
references.pmid: 11500035
references.citation: Muscle Nerve. 2002 Oct;26(4):459-70
references.pmid: 12362410
references.citation: PLoS One. 2011;6(6):e20582
references.pmid: 21687686
references.citation: Brain Res. 2004 Apr 2;1003(1-2):199-204
references.pmid: 15019581
references.citation: Neurology. 2014 Sep 16;83(12 ):1067-74
references.pmid: 25122207
references.citation: PLoS One. 2012;7(6):e39216
references.pmid: 22720079
references.citation: Curr Opin Neurol. 2009 Oct;22(5):486-92
references.pmid: 19593125
references.citation: Biochem Biophys Res Commun. 1996 Nov 1;228(1):29-37
references.pmid: 8912632
references.citation: Neurobiol Dis. 2010 Mar;37(3):493-502
references.pmid: 19833209
references.citation: J Comp Neurol. 2000 Jan 3;416(1):112-25
references.pmid: 10578106
references.citation: J Neuroinflammation. 2010 Jan 28;7:8
references.pmid: 20109233
references.citation: J Neurosci. 2011 Mar 16;31(11):4166-77
references.pmid: 21411657
references.citation: Lancet Neurol. 2011 Mar;10(3):253-63
references.pmid: 21349440
references.citation: Nat Rev Neurosci. 2001 Nov;2(11):806-19
references.pmid: 11715057
references.citation: Mol Neurobiol. 2014 Jun;49(3):1435-48
references.pmid: 24390572
references.citation: Acta Myol. 2011 Jun;30(1):4-8
references.pmid: 21842586
references.citation: Neurobiol Dis. 2004 Apr;15(3):601-9
references.pmid: 15056468
references.citation: Neuroreport. 2004 Oct 5;15(14 ):2271-4
references.pmid: 15371748
references.citation: Mol Cell Neurosci. 2013 Mar;53:34-41
references.pmid: 23110760
references.citation: Neuroimage Clin. 2015 Jan 19;7:409-14
references.pmid: 25685708
references.citation: Neuromolecular Med. 2007;9(3):216-29
references.pmid: 17914180
references.citation: Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Jun;6(2):111-4
references.pmid: 16036435
references.citation: Lancet. 2011 Mar 12;377(9769):942-55
references.pmid: 21296405
references.citation: Brain Res. 2006 Jun 22;1096(1):180-95
references.pmid: 16737688
references.citation: J Cereb Blood Flow Metab. 2014 May;34(5):785-93
references.pmid: 24496176
references.citation: Immunol Today. 1992 Jun;13(6):219-24
references.pmid: 1627250
references.citation: Ann Neurol. 2004 Feb;55(2):221-35
references.pmid: 14755726
references.citation: Neurology. 2001 Oct 9;57(7):1282-9
references.pmid: 11591849
references.citation: J Nucl Med. 2011 May;52(5):677-80
references.pmid: 21498529
references.citation: PLoS One. 2015 Jul 01;10 (7):e0132159
references.pmid: 26132656
references.citation: Eur J Neurosci. 2007 Oct;26(7):1895-901
references.pmid: 17868365
references.citation: Amyotroph Lateral Scler. 2010;11(1-2):38-45
references.pmid: 20184514
references.citation: Nat Rev Neurol. 2011 Nov;7(11):616-30
references.pmid: 22051914
references.citation: Mol Imaging Biol. 2009 Nov-Dec;11(6):386-98
references.pmid: 19330384
references.citation: Nuklearmedizin. 2013 Dec 13;52(6):250-61
references.pmid: 24337014
references.citation: J Cereb Blood Flow Metab. 2010 Jan;30(1):230-41
references.pmid: 19794397
references.citation: Glia. 1998 Jul;23 (3):249-56
references.pmid: 9633809
references.citation: J Nucl Med. 2009 Mar;50(3):468-76
references.pmid: 19223401
references.citation: Am J Pathol. 1992 Mar;140(3):691-707
references.pmid: 1347673
references.citation: Nucl Med Biol. 2015 Mar;42(3):309-16
references.pmid: 25537727
references.citation: Science. 1994 Jun 17;264(5166):1772-5
references.pmid: 8209258
references.citation: Cell Death Dis. 2014 Jul 17;5:e1331
references.pmid: 25032854
references.citation: PLoS One. 2012;7(12 ):e52941
references.pmid: 23300829
references.citation: Neurosci Lett. 2002 Oct 31;332(2):99-102
references.pmid: 12384220
references.citation: Exp Neurol. 2006 Oct;201(2):293-300
references.pmid: 16740261
references.citation: Nucl Med Biol. 2012 May;39(4):570-8
references.pmid: 22172392
references.citation: Appl Radiat Isot. 2012 Mar;70(3):489-97
references.pmid: 22104496
references.citation: Pharmacol Ther. 2008 Apr;118(1):1-17
references.pmid: 18374421