Imaging human brown adipose tissue under room temperature conditions with ¹¹C-MRB, a selective norepinephrine transporter PET ligand

Introduction 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 ¹¹C-MRB ((S,S)-¹¹C-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 ± 2.7 kg/m²; 5 F: age 25.4 ± 2.1, BMI 22.1 ± 1.0 kg/m²) underwent ¹¹C-MRB PET-CT imaging for cervical/supraclavicular BAT under RT and cold-stimulated conditions (RPCM Cool vest; enthalpy 15 °C) compared to ¹⁸F-FDG PET-CT imaging. Uptake of ¹¹C-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, ¹⁸F-FDG uptake in BAT was difficult to identify at RT but easily detected with cold stimulation (p = 0.01). In contrast, BAT ¹¹C-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 ¹¹C-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 ¹⁸F-FDG (p = 0.63). Furthermore, there were gender differences in ¹¹C-MRB uptake in response to cold (p = 0.03), which reflected significant differences in the change in ¹¹C-MRB as a function of both body composition and body temperature. Conclusions Unlike ¹⁸F-FDG, the uptake of ¹¹C-MRB in BAT offers a unique opportunity to investigate the role of BAT in humans under basal, room temperature conditions.