ATP synthase is a promising target for identifying activated and non-activated adipose tissues.

Adipose tissue has gained increasing attention as a therapeutic target to combat human obesity and related metabolic disorders. We propose ATP synthase as a target to identify activated and non-activated adipose tissue. We investigated ATP synthase using the radiotracer [11C]J147 and confirmed the specificity of the radiotracer by in vitro autoradiography, cell knockdown studies, and in vivo competition binding studies. In addition to the interscapular brown adipose tissue (BAT), [11C]J147 could visualise several other BAT depots (supraspinal, infrascapular and axillary BAT) via in vivo positron emission tomography imaging after activation with a β3-adrenergic receptor agonist, as confirmed by immunohistochemistry and biodistribution studies. Furthermore, [11C]J147 demonstrated higher sensitivity for BAT and WAT (white adipose tissue) identification compared to the commonly used radiotracer [18F]FDG and the mitochondrial complex I tracer [18F]BCPP-EF. Our study uncovers ATP synthase as a promising target for monitoring adipose tissue and [11C]J147 could facilitate drug development for metabolic diseases such as obesity.