title: Neuroimaging of translocator protein in patients with systemic lupus erythematosus: a pilot study using [11C]DPA-713 positron emission tomography.
abstract: Objective Inflammation secondary to autoantibody-mediated effects occurring in multiple organs is a hallmark of systemic lupus erythematosus (SLE). The inflammatory response to SLE-mediated damage in brain parenchyma has been postulated in both normal and cognitively impaired individuals. Our goal is to use molecular imaging to investigate the distribution within the brain of the mitochondrial translocator protein (TSPO) that is upregulated during glial cell activation, and is considered as a marker of brain injury and repair. Methods We sought to characterize TSPO distribution in the brain of SLE patients using positron emission tomography (PET) and [11C]DPA-713 (DPA), a radiopharmaceutical that targets TSPO. We imaged 11 healthy controls and 10 patients with SLE (years of diagnosis: 13.0 ± 7.7), all between the ages of 22 and 52.
  
  
  RESULTS
  Among the nine brain regions studied, no statistically significant increases in DPA binding were observed in SLE. Instead, there was a significant decrease in TSPO distribution in the cerebellum and hippocampus of SLE patients, as compared to healthy controls. Such decreases were most significant in cognitively normal SLE subjects, but showed pseudo-normalization in those with cognitive impairment, due to higher cerebellar and hippocampal DPA binding in the cognitively impaired (versus normal) SLE brain. Conclusions Results from this pilot study suggest a link between diminished regional TSPO expression in the brain of patients with SLE, as well as possible glial cell activation within the cerebellum and hippocampus of cognitively impaired individuals with SLE. Further studies are needed to elucidate how mitochondrial dysfunction and glial cell activation may act together in SLE and SLE-mediated neurocognitive deficits.
authors.affiliation: 1 Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2 Department of Psychiatry, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Coughlin
authors.affiliation: 1 Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Shuangchao
authors.initials: S
authors.lastname: Ma
authors.affiliation: 1 Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Endres
authors.affiliation: 3 School of Chemistry, University of Sidney, Sydney, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: 2 Department of Psychiatry, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: 1 Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.affiliation: 4 Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.affiliation: 1 Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|2 Department of Psychiatry, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000081:Acetamides / Q000008:administration & dosage*; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D016022:Case-Control Studies; D003071:Cognition; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000523:psychology; D020945:Lupus Vasculitis, Central Nervous System / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000523:psychology; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D059906:Neuroimaging / Q000379:methods*; D057805:Pets; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011720:Pyrazoles / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D018079:Receptors, GABA / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000081:Acetamides; D015415:Biomarkers; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: Brain; cerebellum; cognitive impairment; glial cell activation; hippocampus; lupus; mitochondria; mitochondrial translocator protein; molecular imaging; neurocognitive deficits; positron emission tomography; systemic lupus erythematosus; translocator protein