Quantification of Human and Rodent Brown Adipose Tissue Function Using ^sup 99m^Tc-Methoxyisobutylisonitrile SPECT/CT and ^sup 18^F-FDG PET/CT

• Published in: The Journal of nuclear medicine (1978) Vol. 54; no. 11; p. 1896
• Main Authors: Cypess, Aaron M, Doyle, Ashley N, Sass, Christina A, Huang, Tian Lian, Mowschenson, Peter M, Rosen, Harold N, Tseng, Yu-Hua, Palmer, Edwin L, Kolodny, Gerald M
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.11.2013
• Subjects: Body fat; Glucose; Medical imaging; Nuclear medicine
• ISSN: 0161-5505; 1535-5667

For brown adipose tissue (BAT) to be effective at consuming calories, its blood flow must increase enough to provide sufficient fuel to sustain energy expenditure and also transfer the heat created to avoid thermal injury. Here we used a combination of human and rodent models to assess changes in BAT blood flow and glucose utilization. 99mTc-methoxyisobutylisonitrile (MIBI) SPECT (n = 7) and SPECT/CT (n = 74) scans done in adult humans for parathyroid imaging were reviewed for uptake in regions consistent with human BAT. Site-directed biopsies of subcutaneous and deep neck fat were obtained for electron microscopy and gene expression profiling. In mice, tissue perfusion was measured with 99mTc-MIBI (n = 16) and glucose uptake with 18F-FDG (n = 16). Animals were kept fasting overnight, anesthetized with pentobarbital, and given intraperitoneally either the ...3-adrenergic receptor agonist CL-316,243, 1 mg/kg (n = 8), or saline (n = 8) followed by radiotracer injection 5 min later. After 120 min, the mice were imaged using SPECT/CT or PET/CT. Vital signs were recorded over 30 min during the imaging. BAT, white adipose tissue (WAT), muscle, liver, and heart were resected, and tissue uptake of both 99mTc-MIBI and 18F-FDG was quantified by percentage injected dose per gram of tissue and normalized to total body weight. In 5.4% of patients (4/74), 99mTc-MIBI SPECT/CT showed increased retention in cervical and supraclavicular fat that displayed multilocular lipid droplets, dense capillary investment, and a high concentration of ovoid mitochondria. Expression levels of the tissue-specific uncoupling protein-1 were 180 times higher in BAT than in subcutaneous WAT (P < 0.001). In mice, BAT tissue perfusion increased by 61% (P < 0.01), with no significant changes in blood flow to WAT, muscle, heart, or liver. CL-316,243 increased glucose uptake in BAT even more, by 440% (P < 0.01). Pharmacologic activation of BAT requires increased blood flow to deliver glucose and oxygen for thermogenesis. However, the glucose consumption far exceeds the vascular response. These findings demonstrate that activated BAT increases glucose uptake beyond what might occur by increased blood flow alone and suggest that activated BAT likely uses glucose for nonthermogenic purposes. (ProQuest: ... denotes formulae/symbols omitted.)