Evaluation of Spleen Glucose Metabolism Using <sup>18</sup>F-FDG PET/CT in Patients with Febrile Autoimmune Disease

Ahn, Sung Soo; Hwang, Sang Hyun; Jung, Seung Min; Lee, Sang Won; Park, Yong Bum; Yun, Mijin; Song, Jason Jungsik

doi:10.2967/jnumed.116.180729

Cited by 34 publications

(34 citation statements)

References 23 publications

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“…As shown in this work, without an appreciation that traditional normalization methods such as SUV and TBR Blood may not be expected to effectively correct for a common dynamic influence of blood in all these tissues, such associations may cause confusion. An argument can be made to use the liver rather than the spleen as a background reference tissue for this purpose due to recent evidence that the spleen activity is related to systemic inflammation [ 32 ], its well-described and clinically established use in oncology [ 23 ], and its more common use as a background reference in vasculitis imaging [ 24 , 33 ]. Additionally, serologic or imaging markers are available if liver dysfunction is suspected.…”

Section: Discussionmentioning

confidence: 99%

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials

et al. 2017

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Introduction18Fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake in the artery wall correlates with active inflammation. However, in part due to the low spatial resolution of PET, variation in the apparent arterial wall signal may be influenced by variation in blood FDG activity that cannot be fully corrected for using typical normalization strategies. The purpose of this study was to evaluate the ability of the current common methods to normalize for blood activity and to investigate alternative methods for more accurate quantification of vascular inflammation.Materials and methodsThe relationship between maximum FDG aorta wall activity and mean blood activity was evaluated in 37 prospectively enrolled subjects aged 55 years or more, treated for hyperlipidemia. Target maximum aorta standardized uptake value (SUV) and mean background reference tissue activity (blood, spleen, liver) were recorded. Target-to-background ratios (TBR) and arterial maximum activity minus blood activity were calculated. Multivariable regression was conducted, predicting uptake values based on variation in background reference and target tissue FDG uptake; adjusting for gender, age, lean body mass (LBM), blood glucose, blood pool activity, and glomerular filtration rate (GFR), where appropriate.ResultsBlood pool activity was positively associated with maximum artery wall SUV (β = 5.61, P<0.0001) as well as mean liver (β = 6.23, P<0.0001) and spleen SUV (β = 5.20, P<0.0001). Artery wall activity divided by blood activity (TBRBlood) or subtraction of blood activity did not remove the statistically significant relationship to blood activity. Blood pool activity was not related to TBRliver and TBRspleen (β = −0.36, P = NS and β = −0.58, P = NS, respectively)ConclusionsIn otherwise healthy individuals treated for hyperlipidemia, blood FDG activity is associated with artery wall activity. However, variation in blood activity may mask artery wall signal reflective of inflammation, which requires normalization. Blood-based TBR and subtraction do not sufficiently adjust for blood activity. Warranting further investigation, background reference tissues with cellular uptake such as the liver and spleen may better adjust for variation in blood activity to improve assessment of vascular activity.

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Section: Discussionmentioning

confidence: 99%

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials

et al. 2017

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“…NK cells in peripheral blood usually rely on an abundance of glucose and oxygen, as blood glucose and oxygen levels are tightly regulated in healthy individuals. In contrast, glucose and oxygen levels in tissues need to be constantly replenished via the bloodstream, a process that can be affected by blood circulation, inflammation or tumor infiltration, resulting in local differences of nutrient levels [ 20 , 21 ]. Many tumor cells possess the ability to significantly increase their glucose uptake, thus decreasing glucose availability for immune cells in their surroundings as a mechanism of immune evasion [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71

et al. 2018

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Metabolism is a critical basis for immune cell functionality. It was recently shown that NK cell subsets from peripheral blood modulate their expression of nutrient receptors following cytokine stimulation, demonstrating that NK cells can adjust to changes in metabolic requirements. As nutrient availability in blood and tissues can significantly differ, we examined NK cells isolated from paired blood-liver and blood-spleen samples and compared expression of the nutrient transporters Glut1, CD98 and CD71. CD56bright tissue-resident (CXCR6+) NK cells derived from livers and spleens expressed lower levels of Glut1 but higher levels of the amino acid transporter CD98 following stimulation than CD56bright NK cells from peripheral blood. In line with that, CD56dim NK cells, which constitute the main NK cell population in the peripheral blood, expressed higher levels of Glut1 and lower levels of CD98 and CD71 compared to liver CD56bright NK cells. Our results show that NK cells from peripheral blood differ from liver- and spleen-resident NK cells in the expression profile of nutrient transporters, consistent with a cell-adaptation to the different nutritional environment in these compartments.

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“…Alshammari et al reported that F18-FDG uptake can be detected not only in the generalized lymph nodes but also in the spleen in patients with KFD [24]. Another study reported that the spleen showed increased F18-FDG uptake in patients with febrile autoimmune disease and is associated with an increased risk of allcause in-hospital mortality [22].…”

Section: Discussionmentioning

confidence: 99%

“…The spleen is an important immune organ in both innate and adaptive immune responses and in regulating immune homeostasis [19]. Studies have shown diffuse increased splenic F18-FDG uptake in lymphoma, infection, tuberculosis, and autoimmune diseases [20][21][22][23]. Moreover, recent findings suggest that a diffuse increased FDG uptake was observed not only in lymph nodes but also in the spleen in patients with KFD [24,25].…”

Section: Introductionmentioning

confidence: 99%

Increased uptake of fluorine-18 fluoro-2-deoxy-D-glucose (F18-FDG) in the spleen: A novel marker for severe Kikuchi-Fujimoto disease

Seong¹,

Jeong²,

Ji³

et al. 2020

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Background: Kikuchi-Fujimoto disease (KFD), known as histiocytic necrotizing lymphadenitis, is an Asian-endemic disease of unknown etiology. Although KFD is usually self-limiting and benign, patients with prolonged systemic symptoms often have frequent hospital visits, long admission durations, and missed workdays. Immune-modulating drugs are used to shorten the clinical course in severe KFD. However, as there are no established severity markers, administration of these drugs is often arbitrary or delayed. We aimed to investigate the role of fluorine-18 fluoro-2-deoxy-D-glucose (F18-FDG) positron emission tomography/computed tomography (F18-FDG PET/CT) in KFD and to evaluate its performance as a disease severity marker. We retrospectively reviewed medical records of 31 adult patients with pathologically confirmed KFD who underwent F18-FDG PET/CT between November 2007 and April 2018 at a tertiary care referral hospital. Disease severity was assessed using the criteria based on clinical manifestations of advanced KFD. The number of systemic activated lymph nodes and severity of splenic activation were determined using semi-quantitative and volumetric PET/CT parameters. Results: The median value of the mean splenic standardized uptake value (SUV mean ) was higher in the 23 patients with severe KFD (1.79±0.99 vs. 2.38±1.18, p =0.058). Patients with severe KFD presented with more systemically activated volume and glycolytic activity than those with mild KFD (total lesion glycolysis: 473.5±504.4 vs 201.6±363.5, p =0.024). Multivariate logistic regression showed that myalgia (odds ratio [OR], 0.035; 95% confidence interval [CI], 0.001-0.792; p =0.035), total lymph node SUV max (cutoff, 9.27) (OR, 24.734; 95% CI, 1.323-462.407; p =0.032), and spleen SUV mean (cutoff, 1.79) (OR, 37.770; 95% CI, 1.769-806.583; p =0.020) were significantly associated with severe KFD. Conclusions: We suggest that 18 F-FDG PET/CT can be a useful tool for clinical workup in the predicting clinical course of KFD as a complement to laboratory and clinical findings to establish the severity.

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Evaluation of Spleen Glucose Metabolism Using ¹⁸F-FDG PET/CT in Patients with Febrile Autoimmune Disease

Cited by 34 publications

References 23 publications

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials

Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71

Increased uptake of fluorine-18 fluoro-2-deoxy-D-glucose (F18-FDG) in the spleen: A novel marker for severe Kikuchi-Fujimoto disease

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Evaluation of Spleen Glucose Metabolism Using 18F-FDG PET/CT in Patients with Febrile Autoimmune Disease

Cited by 34 publications

References 23 publications

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials

Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71

Increased uptake of fluorine-18 fluoro-2-deoxy-D-glucose (F18-FDG) in the spleen: A novel marker for severe Kikuchi-Fujimoto disease

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Evaluation of Spleen Glucose Metabolism Using ¹⁸F-FDG PET/CT in Patients with Febrile Autoimmune Disease