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Intense (18)F-FDG uptake in brown fat can be reduced pharmacologically. 2004

Mitsuaki Tatsumi, and James M Engles, and Takayoshi Ishimori, and O'Bod Nicely, and Christian Cohade, and Richard L Wahl
Division of Nuclear Medicine, Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.

Physiologic (18)F-FDG uptake in areas of supraclavicular fat in humans ("USA-Fat") has recently been recognized as (18)F-FDG uptake in apparent brown adipose tissue (BAT) using fused PET/CT technology. In this study, we evaluated (18)F-FDG uptake in BAT of rats to determine whether pharmacologic or physiologic interventions affect the uptake, knowing that BAT has a high density of adrenergic innervation. METHODS Seven- to 8-wk-old female Lewis rats receiving intravenous (18)F-FDG injections were examined under various conditions to evaluate (18)F-FDG biodistribution into interscapular BAT and major organs. In series 1, rats were given ketamine-based anesthesia or were exposed to cold (4 degrees C for 4 h) to determine whether these interventions increased (18)F-FDG uptake in BAT. In series 2, anesthetized rats (ketamine-based anesthesia) were given propranolol, reserpine, or diazepam intraperitoneally before (18)F-FDG injection to determine whether the drug reduced (18)F-FDG uptake in BAT. The control and treated groups in series 2 were also evaluated with (18)F-FDG PET/CT imaging. RESULTS In series 1, anesthesia or exposure to cold increased (18)F-FDG uptake in BAT to levels 14-fold and 4.9-fold, respectively, greater than the control nonstimulated values. BAT uptake was high, comparable to that in the brain. In series 2, (18)F-FDG uptake in BAT was significantly decreased to less than 30% of the control level after propranolol or reserpine (P < 0.05). Diazepam did not significantly decrease (18)F-FDG uptake in BAT. (18)F-FDG PET/CT findings reflected these biodistribution data: The control and diazepam groups exhibited intense (18)F-FDG uptake in BAT, whereas the propranolol and reserpine groups showed only faint to mild (18)F-FDG uptake in BAT. Among several organs whose (18)F-FDG uptake was affected after predosing drugs, the heart exhibited considerable decreases in tracer uptake with propranolol or reserpine. CONCLUSIONS This rodent study demonstrated that BAT can exhibit high (18)F-FDG uptake under stimulated conditions including exposure to cold and that propranolol or reserpine treatment can remarkably reduce the high (18)F-FDG uptake in BAT. The effect of these drugs on (18)F-FDG uptake in human BAT, as well as on tracer accumulation in other organs, should carefully be evaluated clinically to minimize the USA-Fat artifact.

UI MeSH Term Description Entries
D007649 Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors. 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011433 Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs. Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D012110 Reserpine An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. Raunervil,Raupasil,Rausedil,Rausedyl,Serpasil,Serpivite,V-Serp,V Serp
D002001 Adipose Tissue, Brown A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids. Brown Fat,Hibernating Gland,Brown Adipose Tissue,Fat, Brown,Tissue, Brown Adipose
D003080 Cold Temperature An absence of warmth or heat or a temperature notably below an accustomed norm. Cold,Cold Temperatures,Temperature, Cold,Temperatures, Cold
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D005260 Female Females
D000075 Acepromazine A phenothiazine that is used in the treatment of PSYCHOSES. Acetazine,Acetopromazine,Acetylpromazine,Acepromazine Maleate,Calmivet,Plegicil,Vetranquil,Maleate, Acepromazine
D000758 Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.

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