title: Imaging human brown adipose tissue under room temperature conditions with (11)C-MRB, a selective norepinephrine transporter PET ligand.
abstract: BACKGROUND
  Brown adipose tissue (BAT) plays a critical role in adaptive thermogenesis and is tightly regulated by the sympathetic nervous system (SNS). However, current BAT imaging modalities require cold stimulation and are often unreliable to detect BAT in the basal state, at room temperature (RT). We have shown previously that BAT can be detected in rodents under both RT and cold conditions with (11)C-MRB ((S,S)-(11)C-O-methylreboxetine), a highly selective ligand for the norepinephrine transporter (NET). Here, we evaluate this novel approach for BAT detection in adult humans under RT conditions.
  
  
  METHODS
  Ten healthy, Caucasian subjects (5 M: age 24.6±2.6, BMI 21.6±2.7kg/m(2); 5 F: age 25.4±2.1, BMI 22.1±1.0kg/m(2)) underwent (11)C-MRB PET-CT imaging for cervical/supraclavicular BAT under RT and cold-stimulated conditions (RPCM Cool vest; enthalpy 15°C) compared to (18)F-FDG PET-CT imaging. Uptake of (11)C-MRB, was quantified as the distribution volume ratio (DVR) using the occipital cortex as a low NET density reference region. Total body fat and lean body mass were assessed via bioelectrical impedance analysis.
  
  
  RESULTS
  As expected, (18)F-FDG uptake in BAT was difficult to identify at RT but easily detected with cold stimulation (p=0.01). In contrast, BAT (11)C-MRB uptake (also normalized for muscle) was equally evident under both RT and cold conditions (BAT DVR: RT 1.0±0.3 vs. cold 1.1±0.3, p=0.31; BAT/muscle DVR: RT 2.3±0.7 vs. cold 2.5±0.5, p=0.61). Importantly, BAT DVR and BAT/muscle DVR of (11)C-MRB at RT correlated positively with core body temperature (r=0.76, p=0.05 and r=0.92, p=0.004, respectively), a relationship not observed with (18)F-FDG (p=0.63). Furthermore, there were gender differences in (11)C-MRB uptake in response to cold (p=0.03), which reflected significant differences in the change in (11)C-MRB as a function of both body composition and body temperature.
  
  
  CONCLUSIONS
  Unlike (18)F-FDG, the uptake of (11)C-MRB in BAT offers a unique opportunity to investigate the role of BAT in humans under basal, room temperature conditions.
authors: Division of Endocrinology, Yale University School of Medicine.
authors: Janice J
authors: JJ
authors: Hwang
authors: Yale School of Public Health.
authors: Catherine W
authors: CW
authors: Yeckel
authors: Department of Radiology, Yale PET Center, Yale University School of Medicine.
authors: Jean-Dominique
authors: JD
authors: Gallezot
authors: Division of Endocrinology, Yale University School of Medicine.
authors: Renata Belfort-De
authors: RB
authors: Aguiar
authors: Department of Radiology, Yale PET Center, Yale University School of Medicine.
authors: Devrim
authors: D
authors: Ersahin
authors: Department of Radiology, Yale PET Center, Yale University School of Medicine.
authors: Hong
authors: H
authors: Gao
authors: Department of Radiology, Yale PET Center, Yale University School of Medicine.
authors: Michael
authors: M
authors: Kapinos
authors: Department of Radiology, Yale PET Center, Yale University School of Medicine.
authors: Nabeel
authors: N
authors: Nabulsi
authors: Department of Radiology, Yale PET Center, Yale University School of Medicine.
authors: Yiyun
authors: Y
authors: Huang
authors: Department of Radiology, Yale PET Center, Yale University School of Medicine.
authors: David
authors: D
authors: Cheng
authors: Department of Radiology, Yale PET Center, Yale University School of Medicine.
authors: Richard E
authors: RE
authors: Carson
authors: Division of Endocrinology, Yale University School of Medicine.
authors: Robert
authors: R
authors: Sherwin
authors: Departments of Radiology and Psychiatry, New York University School of Medicine. Electronic address: yu-shin.ding@nyumc.org.
authors: Yu-Shin
authors: YS
authors: Ding
mesh_terms: D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging*; D000328:Adult; D001831:Body Temperature; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D000077593:Reboxetine; D012727:Sex Characteristics; D013696:Temperature; D055815:Young Adult
chemical_list: D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C524178:O-methyl reboxetine; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000077593:Reboxetine
keywords: (S,S)-(11)C-O-methylreboxetine; Human brown adipose tissue; Norepinephrine transporter; Positron emission tomography (PET); Sympathetic nervous system