RT Journal Article
SR Electronic
T1 The Cannabinoid Receptor-1 Is an Imaging Biomarker of Brown Adipose Tissue
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1937
OP 1941
DO 10.2967/jnumed.115.156422
VO 56
IS 12
A1 Olof Eriksson
A1 Kirsi Mikkola
A1 Daniel Espes
A1 Lauri Tuominen
A1 Kirsi Virtanen
A1 Sarita Forsbäck
A1 Merja Haaparanta-Solin
A1 Jarmo Hietala
A1 Olof Solin
A1 Pirjo Nuutila
YR 2015
UL http://jnm.snmjournals.org/content/56/12/1937.abstract
AB Recently, the existence of significant deposits of brown adipose tissue (BAT) in human adults was confirmed. Its role in the human metabolism is unknown but could be substantial. Inhibition of the cannabinoid receptor-1 (CB1) by the antagonist rimonabant (SR141716) has been associated with activation of BAT thermogenesis and weight loss in mice and rats. The role of peripheral and central CB1 in the activation of BAT merits further investigation. Here we developed a technique for quantifying CB1 in BAT by PET. Methods: Sections of rat BAT and subcutaneous white adipose tissue (WAT) were stained for CB1 and uncoupling protein-1 by immunofluorescent staining. Binding of the radiolabeled CB1 antagonist (3R,5R)-5-(3-(18F-fluoromethoxy)phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)-phenyl)pyrrolidin-2-one (18F-FMPEP-d2) to BAT in vivo and in vitro was assessed in rats by PET. Results: We found that CB1 was colocalized with uncoupling protein-1 in BAT, but neither protein was found in WAT. Binding of the radiotracer to BAT sections (but not WAT) in vitro was high and displaceable by pretreatment with rimonabant. Deposits of BAT in rats had significant binding of 18F-FMPEP-d2 in vivo, indicating high CB1 density. WAT deposits were negative for 18F-FMPEP-d2, consistent with the immunofluorescent staining and in vitro results. Conclusion: 18F-FMPEP-d2 PET can quantify CB1 density noninvasively in vivo in rats. CB1 is therefore a promising surrogate imaging biomarker for assessing the presence of BAT deposits as well as for elucidating the mechanism of CB1 antagonist–mediated weight loss.