PT  - JOURNAL ARTICLE
AU  - Olof Eriksson
AU  - Kirsi Mikkola
AU  - Daniel Espes
AU  - Lauri Tuominen
AU  - Kirsi Virtanen
AU  - Sarita Forsbäck
AU  - Merja Haaparanta-Solin
AU  - Jarmo Hietala
AU  - Olof Solin
AU  - Pirjo Nuutila
TI  - The Cannabinoid Receptor-1 Is an Imaging Biomarker of Brown Adipose Tissue
AID  - 10.2967/jnumed.115.156422
DP  - 2015 Dec 01
TA  - Journal of Nuclear Medicine
PG  - 1937--1941
VI  - 56
IP  - 12
4099  - http://jnm.snmjournals.org/content/56/12/1937.short
4100  - http://jnm.snmjournals.org/content/56/12/1937.full
SO  - J Nucl Med2015 Dec 01; 56
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.