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The Cannabinoid Rec...
The Cannabinoid Receptor-1 Is an Imaging Biomarker of Brown Adipose Tissue
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- Eriksson, Olof (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.;Abo Akad Univ, Dept Biosci, Turku, Finland.
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- Mikkola, Kirsi (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.
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- Espes, Daniel (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Tuominen, Lauri (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.;Univ Turku, Dept Psychiat, FI-20521 Turku, Finland.
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- Virtanen, Kirsi (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.
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- Forsbaeck, Sarita (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.
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- Haaparanta-Solin, Merja (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.
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- Hietala, Jarmo (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.;Univ Turku, Dept Psychiat, FI-20521 Turku, Finland.
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- Solin, Olof (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.;Abo Akad Univ, Accelerator Lab, Turku, Finland.
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- Nuutila, Pirjo (author)
- Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland.;Turku Univ Hosp, Dept Endocrinol, FIN-20520 Turku, Finland.
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Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland;Abo Akad Univ, Dept Biosci, Turku, Finland. Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland. (creator_code:org_t)
- 2015-09-10
- 2015
- English.
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:12, s. 1937-1941
- Related links:
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http://jnm.snmjourna...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Subject headings
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- 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 (F-18-FMPEP-d(2)) 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 F-18-FMPEP-d(2) in vivo, indicating high CB1 density. WAT deposits were negative for F-18-FMPEP-d(2), consistent with the immunofluorescent staining and in vitro results. Conclusion: F-18-FMPEP-d(2) 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Keyword
- brown adipose tissue
- cannabinoid 1 receptor
- F-18-FMPEP-d(2)
- positron emission tomography
Publication and Content Type
- ref (subject category)
- art (subject category)
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