18F-fluorobenzyl triphenyl phosphonium: a noninvasive sensor of brown adipose tissue thermogenesis.

Abstract

Recent studies have proposed activation of brown adipose tissue (BAT) thermogenesis as a new strategy to combat obesity. Currently, there is no effective noninvasive imaging agent to directly detect unstimulated BAT and quantify the core mechanism of mitochondrial thermogenesis. We investigated an approach to detect BAT depots and monitor thermogenesis using the mitochondria-targeting voltage sensor radiolabeled fluorobenzyltriphenyl phosphonium (FBnTP). (18)F-FBnTP, (14)C-FBnTP, (18)F-FDG, and (99m)Tc-sestamibi uptake in BAT at room temperature (n = 8) and cold-treated (n = 8) Lewis rats was assayed. The effect of the cold condition on (18)F-FBnTP retention in BAT was assessed in 8 treated and 16 control rats. The effect of the noradrenergic inhibitor propranolol on (14)C-FBnTP response to cold stimulation was investigated in an additional 8 treated and 8 control mice. At room temperature, (18)F-FBnTP accumulated in BAT to an extent similar to that in the heart, second only to the kidney and twice as much as (99m)Tc-sestamibi. Prior exposure to cold (4°C) for 4 h resulted in an 82% decrease of (14)C-FBnTP uptake and an 813% increase of (18)F-FDG uptake in BAT. (99m)Tc-sestamibi uptake was not affected by cold. Administration of (18)F-FBnTP at room temperature 60 min before 120 and 240 min of exposure to cold resulted in marked washout of the tracer from BAT. Propranolol significantly diminished the effect of cold on (14)C-FBnTP and (18)F-FDG uptake into BAT. The intense uptake of (18)F-FBnTP into BAT at room temperature and the response to cold stimulation suggest the unique potential advantage of (18)F-FBnTP not only in detecting unstimulated BAT at high contrast but also in quantifying the mitochondrial thermogenic activity. (18)F-FBnTP PET may serve as a useful technique to assess BAT volume and function.