TY - JOUR
T1 - Neuroimaging of translocator protein in patients with systemic lupus erythematosus
T2 - A pilot study using [11C]DPA-713 positron emission tomography
AU - Wang, Yuchuan
AU - Coughlin, Jennifer M.
AU - Ma, Shuangchao
AU - Endres, Christopher J.
AU - Kassiou, Michael
AU - Sawa, Akira
AU - Dannals, Robert F.
AU - Petri, Michelle
AU - Pomper, Martin G.
N1 - Publisher Copyright:
© SAGE Publications.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
KW - Brain
KW - cerebellum
KW - cognitive impairment
KW - glial cell activation
KW - hippocampus
KW - lupus
KW - mitochondria
KW - mitochondrial translocator protein
KW - molecular imaging
KW - neurocognitive deficits
KW - positron emission tomography
KW - systemic lupus erythematosus
KW - translocator protein
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U2 - 10.1177/0961203316657432
DO - 10.1177/0961203316657432
M3 - Article
C2 - 27387599
AN - SCOPUS:85007275369
SN - 0961-2033
VL - 26
SP - 170
EP - 178
JO - Lupus
JF - Lupus
IS - 2
ER -