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Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity.

ABSTRACT: OBJECTIVE:To determine the role of brown adipose tissue (BAT) in cancer activity. MATERIALS AND METHODS:The study group comprised 142 patients (121 female, 21 male; mean age, 49?±?16 years) who underwent F18-FDG PET/CT (PET/CT) for staging or surveillance of cancer and who were BAT-positive on PET/CT. BAT volume by PET/CT, abdominal (visceral and subcutaneous) fat and paraspinous muscle cross-sectional areas (CSA) were assessed. Groups with and without active cancer on PET/CT were compared using a two-sided paired t test. Linear regression analyses between BAT and body composition parameters were performed. RESULTS:There were 62 patients (54 female, eight male) who had active cancer on PET/CT and 80 patients (67 female, 13 male) without active cancer. Groups were similar in age and BMI (p???0.4), abdominal fat and muscle CSA, fasting glucose, and outside temperature at time of scan (p???0.2). Patients who had active cancer on PET/CT had higher BAT volume compared to patients without active cancer (p?=?0.009). In patients without active cancer, BAT was positively associated with BMI and abdominal fat depots (r?=?0.46 to r?=?0.59, p?

SUBMITTER: Bos SA

PROVIDER: S-EPMC6345160 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity.

Bos Stijn A SA Gill Corey M CM Martinez-Salazar Edgar L EL Torriani Martin M Bredella Miriam A MA

Skeletal radiology 20180913 3

<h4>Objective</h4>To determine the role of brown adipose tissue (BAT) in cancer activity.<h4>Materials and methods</h4>The study group comprised 142 patients (121 female, 21 male; mean age, 49 ± 16 years) who underwent F18-FDG PET/CT (PET/CT) for staging or surveillance of cancer and who were BAT-positive on PET/CT. BAT volume by PET/CT, abdominal (visceral and subcutaneous) fat and paraspinous muscle cross-sectional areas (CSA) were assessed. Groups with and without active cancer on PET/CT were ...[more]

PMID: 30215105

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Project description:For brown adipose tissue (BAT) to be effective at consuming calories, its blood flow must increase enough to provide sufficient fuel to sustain energy expenditure and also transfer the heat created to avoid thermal injury. Here we used a combination of human and rodent models to assess changes in BAT blood flow and glucose utilization.(99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT (n = 7) and SPECT/CT (n = 74) scans done in adult humans for parathyroid imaging were reviewed for uptake in regions consistent with human BAT. Site-directed biopsies of subcutaneous and deep neck fat were obtained for electron microscopy and gene expression profiling. In mice, tissue perfusion was measured with (99m)Tc-MIBI (n = 16) and glucose uptake with (18)F-FDG (n = 16). Animals were kept fasting overnight, anesthetized with pentobarbital, and given intraperitoneally either the ?3-adrenergic receptor agonist CL-316,243, 1 mg/kg (n = 8), or saline (n = 8) followed by radiotracer injection 5 min later. After 120 min, the mice were imaged using SPECT/CT or PET/CT. Vital signs were recorded over 30 min during the imaging. BAT, white adipose tissue (WAT), muscle, liver, and heart were resected, and tissue uptake of both (99m)Tc-MIBI and (18)F-FDG was quantified by percentage injected dose per gram of tissue and normalized to total body weight.In 5.4% of patients (4/74), (99m)Tc-MIBI SPECT/CT showed increased retention in cervical and supraclavicular fat that displayed multilocular lipid droplets, dense capillary investment, and a high concentration of ovoid mitochondria. Expression levels of the tissue-specific uncoupling protein-1 were 180 times higher in BAT than in subcutaneous WAT (P < 0.001). In mice, BAT tissue perfusion increased by 61% (P < 0.01), with no significant changes in blood flow to WAT, muscle, heart, or liver. CL-316,243 increased glucose uptake in BAT even more, by 440% (P < 0.01).Pharmacologic activation of BAT requires increased blood flow to deliver glucose and oxygen for thermogenesis. However, the glucose consumption far exceeds the vascular response. These findings demonstrate that activated BAT increases glucose uptake beyond what might occur by increased blood flow alone and suggest that activated BAT likely uses glucose for nonthermogenic purposes.

Project description:BackgroundBrown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [18F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [18F]FDG PET/CT.MethodsWe analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated by mild cold exposure. In cohort 1, we performed [18F]FDG PET/MRI; in cohort 2, we used [18F]FDG PET/CT followed by MRI. Fat fraction was determined by 2-point Dixon and 6-point Dixon measurement, respectively. Fat fraction values were compared to SUVmean in the corresponding tissue depot by simple linear regression.ResultsIn total, 33 male participants with a mean age of 23.9 years and a mean BMI of 22.8 kg/m2 were recruited. In 32 participants, active BAT was visible. On an intra-individual level, FF was significantly lower in high-SUV areas compared to low-SUV areas (cohort 1: p < 0.0001 and cohort 2: p = 0.0002). The FF of the supraclavicular adipose tissue depot was inversely related to its metabolic activity (SUVmean) in both cohorts (cohort 1: R2 = 0.18, p = 0.09 and cohort 2: R2 = 0.42, p = 0.009).ConclusionMRI FF explains only about 40% of the variation in BAT glucose uptake. Thus, it can currently not be used to substitute [18F] FDG PET-based imaging for quantification of BAT activity.Trial registrationClinicalTrials.gov. NCT03189511 , registered on June 17, 2017, actual study start date was on May 31, 2017, retrospectively registered. NCT03269747 , registered on September 01, 2017.

Project description:IntroductionBrown adipose tissue (BAT) becomes the favorite target for preventing and treating metabolic diseases because the activated BAT can produce heat and consume energy. The brain, especially the hypothalamus, which secretes Neuropeptide Y (NPY), is speculated to regulate BAT activity. However, whether NPY is involved in BAT activity's central regulation in humans remains unclear. Thus, it's essential to explore the relationship between brain glucose metabolism and human BAT activity.MethodsA controlled study with a large sample of healthy adults used Positron emission tomography/computed tomography (PET/CT) to noninvasively investigate BAT's activity and brain glucose metabolism in vivo. Eighty healthy adults with activated BAT according to the PET/CT scan volunteered to be the BAT positive group, while 80 healthy adults without activated BAT but with the same gender, similar age, and BMI, scanning on the same day, were recruited as the control (BAT negative). We use Statistical parametric mapping (SPM) to analyze the brain image data, Picture Archiving & Communication System (PACS), and PET/CT Viewer software to calculate the semi-quantitative values of brain glucose metabolism and BAT activity. ELISA tested the levels of fasting plasma NPY. The multiple linear regression models were used to analyze the correlation between brain glucose metabolism, the level of NPY, and the BAT activity in the BAT positive group.Results(1) Compared with controls, BAT positive group showed significant metabolic decreases mainly in the right Insula (BA13a, BA13b) and the right claustrum (uncorrected P <0.01, adjusted BMI). (2) The three brain regions' semi-quantitative values in the BAT positive group were significantly lower than the negative group (all P values < 0.05). (3) After adjusting for age, gender, BMI, and outside temperature, there was a negative correlation between brain metabolic values and BAT activity (all P values < 0.05). However, after further adjusting for NPY level, there were no significant differences between the BA13b metabolic values and BAT activity (P>0.05), while the correlation between the BA13a metabolic values and BAT activity still was significant (P< 0.05).ConclusionsRegional brain glucose metabolism is closely related to healthy adults' BAT activity, which may be mediated by NPY.

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Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity.

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Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity.

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