Imaging brown fat in humans with 11C-MRB, a selective norepinephrine transporter PET ligand

235 Objectives Understanding the role of brown adipose tissue (BAT) in human adaptive thermogenesis has been limited by the current standard detection methodology, 18F-FDG-PET, which requires cold stimulation. Capitalizing on the sympathetic regulation of BAT, we showed that BAT can be detected in rodents under room temperature (RT) and cold conditions with 11C-MRB ((S,S)-11C-O-methylreboxetine), a highly selective norepinephrine transporter ligand. 11C-MRB uptake at RT was correlated with BAT mass (R2=0.945). Here we evaluate this novel approach for BAT detection in adult humans. Methods Ten lean, healthy, Caucasian subjects (5 M; age 25.0±2.2 years; BMI 21.9±2.0 kg/m2) were recruited. Subjects underwent 11C-MRB PET/CT imaging under RT and mild cold-stimulated conditions (RPCM Cool vest; enthalpy 15°C) compared to 18F-FDG PET/CT imaging. Mean standardized uptake value (SUV) for FDG and distribution volume ratio (DVR) for 11C-MRB via MRTM2 using occipital reference region were estimated. DVR(BAT/muscle) was also compared. Results As expected with FDG, BAT was well-defined in the mild cold condition, but difficult to identify in the RT. 9 out of 10 subjects had labeled BAT with cold FDG and both RT and cold MRB scans (BAT DVR: RT 0.99±0.3 vs cold 1.1±0.26, P=0.31; DVR(BAT/muscle): RT 2.28±0.8 vs cold 2.41±0.56, P=0.26). Furthermore, [11C]MRB distribution (RT and cold) occurred in the same neck/supraclavicular locations as the cold 18F-FDG scans. There were no gender differences in BAT labeling. Conclusions By utilizing a novel, mechanistic approach, we show that 11C-MRB labeling of BAT is largely independent of temperature. Thus, 11C-MRB imaging offers a unique opportunity to investigate the role of BAT in humans under non-stimulated basal conditions. Research Support NIDDK 1R21DK09076-01 (Drs. Sherwin and Ding contributed equally to this work as co-principal investigators)