Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Biomedical Engineering Director of Radiology Research University of Southern California Los Angeles, California

BAT: Structure and Function One of two types of adipose tissue (white and brown) Contains smaller fat vacuoles, higher number of mitochondria, more capillaries than white fat Richly innervated by sympathetic nerves (  1,  2,  3) Uncoupling protein-1 (UCP-1, thermogenin) in inner mitochondrial membrane uncouples oxidative phosphorylation producing heat energy (non-shivering thermogenesis) with ATP provided by glycolysis Present in newborns (5% body mass) and hibernating animals; most disappear in adulthood (not in mice) Contribution to evolutionary success of mammals Cannon B et al. Physiol Rev 2004 (Sweden)

BAT: Structure and Function Brown FatWhite Fat

BAT: Structure and Function Hematoxylin-Eosin Hematoxylin & anti-UCP-1 Ab Tatsumi M et al. J Nucl Med 45: , 2004.

BAT: Distribution in Humans Human depots differently located from than those in rodents Main depots: Supraclavicular Fossa (USA-Fat), Axillae, and Neck Mediastinal Paravertebral, Para-aortic, Parahepatic, Paracolic Suprarenal/Perinephric Acutely cold-induced, stimulated by sympathetic nervous system Almost all mediastinal/suprarenal BAT FDG uptake associated with concurrent supraclavicular/paravertebral uptake Neck (2.3%) > Paravertebral (1.4%) > Mediastinum (0.9%) > Perinephric (0.8%), overall (up to 4%) females > males; children > adults (15% vs. 2%) (p<0.01) Hany TF et al. Eur J Nucl Med Mol Imaging 2002 (Switzerland); Yeung HW et al. J Nucl Med 2003 (MSKCC, NY); Cohade C et al J Nucl Med 2003 (Johns Hopkins); Kim S et al. Clin Nucl Med 2006 (Mount Sinai, NY); Nedergaard J et al. Am J Physiol 2007.

Brown Adipose Tissue

BAT: Effect of Cold and Pharmacologic Interventions on FDG Uptake Female Lewis rats injected with FDG under conditions of: Control (no pre-medication and exposure to cold) Exposure to cold (4 C for 4 h) Propranolol, or Reserpine, or Dizepam Cold Exposure: 5x increase in uptake (vs. control) Propranolol or Reserpine: 70% decline in uptake (vs. control) Diazepam: no significant change Tatsumi M et al. J Nucl Med 2004 (Johns Hopkins)

BAT: Effect of Fentanyl and Diazepam on FDG Uptake Gelfand MJ et al. Pediatr Radiol pediatric patients received iv Fentanyl, or low (0.06 mg/kg) or moderate dose (0.1 mg/kg) diazepam prior to PET Visual grading BAT FDG uptake Fentanyl reduced BAT FDG uptake significantly (p=0.004) Low dose diazepam no effect (p=0.98) Medium dose diazepam indeterminate Lower FDG uptake in age 10 y (p=0.02) baseline after fentanyl

BAT: Effect of  -adrenergic agonists on FDG Uptake Female Lewis rats injected with caffeine, ephedrine, or nicotine 30 min before iv FDG Increase in BAT FDG uptake compared to control rats: Ephedrine 3.7x Nicotine 7.9x Nicotine + Ephedrine12.0x Caffeineslight (p=ns) Effects blocked by prior  -adrenergic antagonist “Patients should avoid nicotine, ephedrine before FDG PET” Baba S et al. J Nucl Med 2007 (Johns Hopkins)

BAT: Effect of  -adrenergic antagonists on FDG Uptake 26 patients with FDG PET scans before and after propranolol (20 mg po 60 min prior to iv FDG) No adverse effects in patients or on tumor FDG uptake BAT SUVmax (p<0.0001) Pre-propranolol5.52+/-2.30 Post-propranolol1.39+/-0.42 Post-propranolol scan improved image interpretation most notably in the mediastinum Similar findings with 80 mg propranolol po 2 hrs prior to FDG Parysow O et al. Clin Nucl Med 2007 (Argentina) Soderlund V et al. Eur J Nucl Med Mol Imaging 2007 (Sweden)

BAT: Reduction of FDG Uptake with Warm Temperature Uptake incidence of 13.7% during January through March and 4.1%, during the rest of the year. Warm clothing, avoidance of exposure to cold air during transit to PET facility, temperature-controlled room (75 F) reduces BAT FDG uptake significantly Warm temperature reduces FDG uptake in BAT despite no effect by benzodiazepine Cohade C et al. J Nucl Med 2003 (Johns Hopkins) Garcia CA et al. Mol Imaging Biol 2006 (Washington DC) Garcia CA et al. Mol Imaging Biol 2004 (Washington DC)

BAT: Reduction of FDG Uptake with Warm Temperature Garcia CA et al. Mol Imaging Biol 2006

BAT and FDG Uptake: Summary Non-shivering thermogenesis Function of age, sex, ambient temperature, sympathetic nervous system Supraclavicular, Axillae, Neck, Mediastinum, Paravertebral, Para- aortic, Parahepatic, Paracolic, Suprarenal, Perinephric Avoid nicotine and sympathetic NS stimulatory agents Can be reduced with warm temperature and pharmacologically Warm clothing, avoidance of exposure to cold, temperature- controlled room (75 F) Propranolol (20 mg orally one hour prior to FDG)